α-Lactosylceramide Protects Against iNKT-Mediated Murine Airway Hyperreactivity and Liver Injury Through Competitive Inhibition of Cd1d Binding.

Invariant natural killer T (iNKT) cells, which are activated by T cell receptor (TCR)-dependent recognition of lipid-based antigens presented by the CD1d molecule, have been shown to participate in the pathogenesis of many diseases, including asthma and liver injury. Previous studies have shown the inhibition of iNKT cell activation using lipid antagonists can attenuate iNKT cell-induced disease pathogenesis. Hence, the development of iNKT cell-targeted glycolipids can facilitate the discovery of new therapeutics. In this study, we synthesized and evaluated α-lactosylceramide (α-LacCer), an α-galactosylceramide (α-GalCer) analog with lactose substitution for the galactose head and a shortened acyl chain in the ceramide tail, toward iNKT cell activation. We demonstrated that α-LacCer was a weak inducer for both mouse and human iNKT cell activation and cytokine production, and the iNKT induction by α-LacCer was CD1d-dependent. However, when co-administered with α-GalCer, α-LacCer inhibited α-GalCer-induced IL-4 and IFN-γ production from iNKT cells. Consequently, α-LacCer also ameliorated both α-GalCer and GSL-1-induced airway hyperreactivity and α-GalCer-induced neutrophilia when co-administered in vivo. Furthermore, we were able to inhibit the increases of ConA-induced AST, ALT and IFN-γ serum levels through α-LacCer pre-treatment, suggesting α-LacCer could protect against ConA-induced liver injury. Mechanistically, we discerned that α-LacCer suppressed α-GalCer-stimulated cytokine production through competing for CD1d binding. Since iNKT cells play a critical role in the development of AHR and liver injury, the inhibition of iNKT cell activation by α-LacCer present a possible new approach in treating iNKT cell-mediated diseases

Stringy Symmetries and Their High-energy Limits

We derive stringy symmetries with conserved charges of arbitrarily high spins from the decoupling of two types of zero-norm states in the old covariant first quantized (OCFQ) spectrum of open bosonic string. These symmetries are valid to all energy and all loop orders in string perturbation theory. The high-energy limit of these stringy symmetries can then be used to fix the proportionality constants between scattering amplitudes of different string states algebraically without referring to Gross and Mende's saddle point calculation of high-energy string-loop amplitudes. These proportionality constants are, as conjectured by Gross, independent of the scattering angle and the order of string perturbation theory. However, we also discover some new nonzero components of high-energy amplitudes not found previously by Gross and Manes. These components are essential to preserve massive gauge invariances or decouple massive zero-norm states of string theory. A set of massive scattering amplitudes and their high energy limit are calculated explicitly to justify our results.Comment: 10 pages. A corrected version of hep-th/0303012. Final version to appear in Phys. Lett.

Zero-norm states and High-energy Symmetries of String Theory

We derive stringy Ward identities from the decoupling of two types of zero-norm states in the old covariant first quantized (OCFQ) spectrum of open bosonic string. These Ward identities are valid to all energy and all loop orders in string perturbation theory. The high-energy limit of these stringy Ward identities can then be used to fix the proportionality constants between scattering amplitudes of different string states algebraically without referring to Gross and Mende's saddle point calculation of high-energy string-loop amplitudes. As examples, all Ward identities for the mass level 4 and 6 are derived, their high-energy limits are calculated and the proportionality constants between scattering amplitudes of different string states are determined. In addition to those identified before, we discover some new nonzero components of high-energy amplitudes not found previously by Gross and Manes. These components are essential to preserve massive gauge invariances or decouple massive zero-norm states of string theory. A set of massive scattering amplitudes and their high energy limits are calculated explicitly for each mass level to justify our results

POINeT: protein interactome with sub-network analysis and hub prioritization

<p>Abstract</p> <p>Background</p> <p>Protein-protein interactions (PPIs) are critical to every aspect of biological processes. Expansion of all PPIs from a set of given queries often results in a complex PPI network lacking spatiotemporal consideration. Moreover, the reliability of available PPI resources, which consist of low- and high-throughput data, for network construction remains a significant challenge. Even though a number of software tools are available to facilitate PPI network analysis, an integrated tool is crucial to alleviate the burden on querying across multiple web servers and software tools.</p> <p>Results</p> <p>We have constructed an integrated web service, POINeT, to simplify the process of PPI searching, analysis, and visualization. POINeT merges PPI and tissue-specific expression data from multiple resources. The tissue-specific PPIs and the numbers of research papers supporting the PPIs can be filtered with user-adjustable threshold values and are dynamically updated in the viewer. The network constructed in POINeT can be readily analyzed with, for example, the built-in centrality calculation module and an integrated network viewer. Nodes in global networks can also be ranked and filtered using various network analysis formulas, i.e., centralities. To prioritize the sub-network, we developed a ranking filtered method (S3) to uncover potential novel mediators in the midbody network. Several examples are provided to illustrate the functionality of POINeT. The network constructed from four schizophrenia risk markers suggests that EXOC4 might be a novel marker for this disease. Finally, a liver-specific PPI network has been filtered with adult and fetal liver expression profiles.</p> <p>Conclusion</p> <p>The functionalities provided by POINeT are highly improved compared to previous version of POINT. POINeT enables the identification and ranking of potential novel genes involved in a sub-network. Combining with tissue-specific gene expression profiles, PPIs specific to selected tissues can be revealed. The straightforward interface of POINeT makes PPI search and analysis just a few clicks away. The modular design permits further functional enhancement without hampering the simplicity. POINeT is available at <url>http://poinet.bioinformatics.tw/</url>.</p

Notes on High Energy Limit of Bosonic Closed String Scattering Amplitudes

We study bosonic closed string scattering amplitudes in the high-energy limit. We find that the methods of decoupling of high-energy zero-norm states and the high-energy Virasoro constraints, which were adopted in the previous works to calculate the ratios among high-energy open string scattering amplitudes of different string states, persist for the case of closed string. However, we clarify the previous saddle-point calculation for high-energy open string scattering amplitudes and claim that only (t,u) channel of the amplitudes is suitable for saddle-point calculation. We then discuss three evidences to show that saddle-point calculation for high-energy closed string scattering amplitudes is not reliable. By using the relation of tree-level closed and open string scattering amplitudes of Kawai, Lewellen and Tye (KLT), we calculate the high-energy closed string scattering amplitudes for arbitrary mass levels. For the case of high-energy closed string four-tachyon amplitude, our result differs from the previous one of Gross and Mende, which is NOT consistent with KLT formula, by an oscillating factor.Comment: 14 pages, no figure. Equations and Conclusion adde

Seroprevalence of enterovirus 71 and no evidence of crossprotection of enterovirus 71 antibody against the other enteroviruses in kindergarten children in Taipei city

Background/PurposeEnterovirus 71 (EV71) infection may cause severe neurological and cardiopulmonary complications, especially in preschool children. This study is to investigate the seroprevalence and seroconversion of EV71, and the crossprotection of EV71 antibody against other enteroviruses among kindergarteners.MethodsOverall 228 children in a public kindergarten were enrolled during two academic years, 2006 and 2007, in Taipei, Taiwan and we measured their EV71 neutralizing antibody. When the participants had herpangina; hand, foot and mouth disease (HFMD); febrile illness or respiratory symptoms, throat swabs were sampled and processed for viral culture and enterovirus real-time reverse transcriptase polymerase chain reaction (RT-PCR). Questionnaires, completed by the participants’ guardians, surveyed the history of allergy and annual incidence of symptoms related to enterovirus infection.ResultsSeropositive rates of EV71 were 20% (32/163) in 2006 and 6% (4/65) in 2007. The rate of EV71 seropositivity increased with age (p < 0.01) in 2006 but it did not differ between genders (p = 0.14). No seroconversion was observed from 2006 to 2007. Herpangina occurred in 64% of children with EV71 seropositivity and 48% of those without EV71 antibodies (p = 0.12). Non-71 enterovirus infection, confirmed by viral study, occurred in 53% (19/36) of the EV71-seropositive children and in 53% (102/192) of EV71-seronegative children (p = 0.89). No participants had EV71 infection during the study period.ConclusionEV71 did not frequently circulate in Taipei City from September 2006 to June 2008. Presence of EV71 neutralizing antibody was not associated with lower incidence of enterovirus infection caused by non-71 serotypes

Scatterings of Massive String States from D-brane and Their Linear Relations at High Energies

We study scatterings of bosonic massive closed string states at arbitrary mass levels from D-brane. We discover that all the scattering amplitudes can be expressed in terms of the generalized hypergeometric function with special arguments, which terminates to a finite sum and, as a result, the whole scattering amplitudes consistently reduce to the usual beta function. For the simple case of D-particle, we explicitly calculate high-energy limits of a series of the above scattering amplitudes for arbitrary mass levels, and derive infinite linear relations among them for each fixed mass level. The ratios of these high-energy scattering amplitudes are found to be consistent with the decoupling of high-energy zero-norm states of our previous works.Comment: 19 pages, no figure. v2:some minor corrections, refs added. v3:minor changes and final in Nucl.Phys.