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RAIMUNDUS LULLUS, Ars brevis, trad. ALEXANDER FIDORA. W. KOCH / M. GLASER / F. ALBRECHT BORNSCHLEGEL, Literaturbericht zur mittelalterlichen Epigraphik. BERNOLD VON KONSTANZ, De excommunicatis vitandis, de reconciliatione lapsorum et de fontibus iuris ecclesiastici (Libellus X), ed. DORIS STÖCKLY. MARTÍN KAUFHOLD, Deutsches Interregnum und Europäische Politik. Konfliktlösungen und Entscheudungsstrukturen. 1230-1280. A. FIDORA / A. NIEDERBERGER, Von Bagdad nach Toledo. Das “Buch der Ursachen” und seine Rezeption im Mittelalter. KLAUS RAHNERT, Entmachung der Zeichen? Augustin über Sprache. JÜRGEN MIETHKE, De potestate papae. Die päpstliche Amtskompetenz im Widerstreit der politischen Theorie von Thomas von Aquin bis Wilhem vom Ockham. GIOVANNA CERESOLA, Fantasia e illusione in S. Agostino dai Soliloquia al De Mendacio. CRISTOFORO LANDINO, De vita contemplativa et activa (¿El intelectual o el político?, trad. SILVIA MAGNAVACCA. MARIO SANTIAGO DE CARVALHO, A novidade do mundo: Henrique de Gand e a metafisica da temporalidade no seculo XIII

Superantigens from Staphylococcus aureus induce procoagulant activity and monocyte tissue factor expression in whole blood and mononuclear cells via IL-1beta.

Background: Staphylococcus aureus is one of the most common bacteria in human sepsis, a condition in which the activation of blood coagulation plays a critical pathophysiological role. During severe sepsis and septic shock microthrombi and multiorgan dysfunction are observed as a result of bacterial interference with the host defense and coagulation systems. Objectives: In the present study, staphylococcal superantigens were tested for their ability to induce procoagulant activity and tissue factor (TF) expression in human whole blood and in peripheral blood mononuclear cells. Methods and results: Determination of clotting time showed that enterotoxin A, B and toxic shock syndrome toxin 1 from S. aureus induce procoagulant activity in whole blood and in mononuclear cells. The procoagulant activity was dependent on the expression of TF in monocytes since antibodies to TF inhibited the effect of the toxins and TF was detected on the surface of monocytes by flow cytometry. In the supernatants from staphylococcal toxin-stimulated mononuclear cells, interleukin (IL)-1beta was detected by ELISA. Furthermore, the increased procoagulant activity and TF expression in monocytes induced by the staphylococcal toxins were inhibited in the presence of IL-1 receptor antagonist, a natural inhibitor of IL-1beta. Conclusions: The present study shows that superantigens from S. aureus activate the extrinsic coagulation pathway by inducing expression of TF in monocytes, and that the expression is mainly triggered by superantigen-induced IL-1beta release

IL-2 Regulates SEB Induced Toxic Shock Syndrome in BALB/c Mice

BACKGROUND:Toxic Shock Syndrome (TSS) is characterized by fever, rash, hypotension, constitutional symptoms, and multi-organ involvement and is caused by Staphylococcus aureus enterotoxins such as Staphylococcal Enterotoxin B (SEB). SEB binds to the MHC-IIalpha chain and is recognized by the TCRbeta chain of the Vbeta8 TCR(+) T cells. The binding of SEB to Vbeta chain results in rapid activation of T cells and production of inflammatory cytokines, such as Interleukin-2 (IL-2), Interferon-gamma and Tumor Necrosis Factor-alpha which mediate TSS. Although IL2 was originally identified as the T cell growth factor and was proposed to contribute to T cell differentiation, its role in TSS remains unexplored. METHODOLOGY/PRINCIPAL FINDINGS:Mice were injected with D-Gal (25 mg/mouse). One hour after D-Galactosamine (D-Gal) injection each mouse was injected with SEB (20 microg/mouse. Mice were then observed for 72 hrs and death was recorded at different times. We tested Interleukin-12, IFNgamma, and IL-2 deficient mice (IL-2(-/-)), but only the IL-2 deficient mice were resistant to SEB induced toxic shock syndrome. More importantly reconstitution of IL-2 in IL-2 deficient mice restored the shock. Interestingly, SEB induced IL-2 production from T cells was dependent on p38MAPK activation in macrophages as inhibition of it in macrophages significantly inhibited IL-2 production from T cells. CONCLUSION:This study shows the importance of IL -2 in TSS which has not been previously explored and it also shows that regulating macrophages function can regulate T cells and TSS

Reseñas

Iotsald von Saint-Claude, Vita des Abtes Odilo von Cluny, ed. JOHANNES STAUB. JOHANNES STAUB, Studien zu Iotsalds Vita des Abtes Odilo von Cluny. ANDRÉ JOAO MARIA, Sentido, simbolismo e interpretacao no discurso filosófico de Nicolau de Cusa. WOFGANG D. FRITZ / WOFGANG EGGERT (ed), Monumenta Germaniae Historica. Constitutiones et acta publica imperatorum et regum tomi XI. Fasciculus VIII: Dokumente zur Geschichte des deutschen Reiches und seiner Verfassung 1354-1356. THOMAS FRENZ / PETER HERDE (ed), Das Brief- und Memorialbuch des Albert Behaim. ROMAN DEUTINGER / RAHEWIN VON FREISING, ein Gelehrter des 12. Jahrhunderts. UWE LUDWIG, Transalpine Beziehungen der Karolingerzeit im Spiegel der Memorialüberlieferung. Prosopographische und sozialgeschchtliche Studien unter besonderer Berücksichtigung des “Liber vitae” von San Salvatore in Brescia und des Evangeliars von Cividale. VALENTÍN CRICCO, Semiótica Agustiniana. El diálogo ‘El Maestro’ de san Agustín. VICTORIA CIRLOT / BLANCA GARÍ, La mirada interior. Escritoras místicas y visionarias en la Edad Media. IGNACIO ANGELELLI / PALOMA PÉREZ-ILZARBE (ed), Medieval and renaissance logic in Spain: acts of the 12th European Symposium on Medieval Logic and Semantics, held at the University of Navarre

Mixing and matching siderophore clusters: structure and biosynthesis of serratiochelins from Serratia sp. v4

Studying the evolutionary history underlying the remarkable structures and biological activities of natural products has been complicated by not knowing the functions they have evolved to fulfill. Siderophores - soluble, low molecular weight compounds - have an easily understood and measured function: acquiring iron from the environment. Bacteria engage in a fierce competition for acquiring iron, which rewards the production of siderophores that bind iron tightly and cannot be used or pirated by competitors. The structures and biosyntheses of 'odd' siderophores can reveal the evolutionary strategy that led to their creation. Here, we here report a new Serratia strain that produces serratiochelin and an analog of serratiochelin. A genetic approach located the serratiochelin gene cluster, and targeted mutations in several genes implicated in serratiochelin biosynthesis were generated. Bioinformatic analyses and mutagenesis results demonstrate that genes from two well known siderophore clusters, the Escherichia coli enterobactin cluster and the Vibrio cholerae vibriobactin cluster, were shuffled to produce a new siderophore biosynthetic pathway. These results highlight how modular siderophore gene clusters can be mixed and matched during evolution to generate structural diversity in siderophores.This work was supported by the National Institutes of Health (Grants GM82137 to R.K., and AI057159 and GM086258 to J.C.). M.R.S. acknowledges support from the NIH Pathway to Independence Award (Grant 1K99 GM098299-01). S.C. and M.J.V. acknowledge support from the Portuguese Foundation for Science and Technology (PhD Grant SFRH/BD/38298/2007 to S.C.; Project PTDC/EBB-EBI/104263/2008 to M.J.V.)

A Role for the Immediate Early Gene Product c-fos in Imprinting T Cells with Short-Term Memory for Signal Summation

T cells often make sequential contacts with multiple DCs in the lymph nodes and are likely to be equipped with mechanisms that allow them to sum up the successive signals received. We found that a period of stimulation as short as two hours could imprint on a T cell a “biochemical memory” of that activation signal that persisted for several hours. This was evidenced by more rapid induction of activation markers and earlier commitment to proliferation upon subsequent stimulation, even when that secondary stimulation occurred hours later. Upregulation of the immediate early gene product c-fos, a component of the AP-1 transcription factor, was maximal by 1–2 hours of stimulation, and protein levels remained elevated for several hours after stimulus withdrawal. Moreover, phosphorylated forms of c-fos that are stable and transcriptionally active persisted for a least a day. Upon brief antigenic stimulation in vivo, we also observed a rapid upregulation of c-fos that could be boosted by subsequent stimulation. Accumulation of phosphorylated c-fos may therefore serve as a biochemical fingerprint of previous suboptimal stimulation, leaving the T cell poised to rapidly resume its activation program upon its next encounter with an antigen-bearing DC

Ursodeoxycholic Acid Therapy in Pediatric Primary Sclerosing Cholangitis : Predictors of Gamma Glutamyltransferase Normalization and Favorable Clinical Course

Objective To investigate patient factors predictive of gamma glutamyltransferase (GGT) normalization following ursodeoxycholic acid (UDCA) therapy in children with primary sclerosing cholangitis. Study design We retrospectively reviewed patient records at 46 centers. We included patients with a baseline serum GGT level >= 50 IU/L at diagnosis of primary sclerosing cholangitis who initiated UDCA therapy within 1 month and continued therapy for at least 1 year. We defined "normalization" as a GGT level Results We identified 263 patients, median age 12.1 years at diagnosis, treated with UDCA at a median dose of 15 mg/kg/d. Normalization occurred in 46%. Patients with normalization had a lower prevalence of Crohn's disease, lower total bilirubin level, lower aspartate aminotransferase to platelet ratio index, greater platelet count, and greater serum albumin level at diagnosis. The 5-year survival with native liver was 99% in those patients who achieved normalization vs 77% in those who did not. Conclusions Less than one-half of the patients treated with UDCA have a complete GGT normalization in the first year after diagnosis, but this subset of patients has a favorable 5-year outcome. Normalization is less likely in patients with a Crohn's disease phenotype or a laboratory profile suggestive of more advanced hepatobiliary fibrosis. Patients who do not achieve normalization could reasonably stop UDCA, as they are likely not receiving clinical benefit. Alternative treatments with improved efficacy are needed, particularly for patients with already-advanced disease.Peer reviewe

Reseñas

MARTIN THURNER, Gott als das offenbare Geheimnis nach Nikolaus von Kues, NICOLÁS DE CUSA, Acerca de la docta ignorancia, trad. J. M. MACHETTA / C. D’AMICO. THILO OFFERGELD, Reges pueri. Das Königtum Minderjähriger im Frühen Mittelalter. W. EFFERT (ed), Monumenta Germaniae Historica, Constitutiones et acta publica imperatorum et regum. THOMAS EBENDORFER, Chronica regum Romanorum, ed. H. ZIMMERMANN. MARTIN THURNER (ed), Nicolaus Cusanus zwischen Deutschland und Italien. PEDRO ABELARDO, Diálogo entre un filósofo, un judío y un Cristiano, trad. SILVIA MAGNAVACCA. M. ÁLVAREZ GÓMEZ / J. MARÍA ANDRÉ, Coincidencia de opuestos y concordia. Los caminos del pensamiento en Nicolás de Cusa. J. IGNASI SARANYANA, La filosofía medieval. Desde sus orígenes patrísticos hasta la Escolástica barroca. TOMÁS DE AQUINO-PEDRO DE ALVERNIA, Comentario a la Política de Aristóteles, trad. A. MALLEA. G. FERNÁNDEZ DE OVIEDO, Claribalte, ed. M. J. RODILLA LEÓN. RICCARDO QUINTO, Scholastica. Storia di un concetto. LUIS ALBERTO DE BONI, De Abelardo a Lutero. Estudos sobre filosofia prática na Idade Media. O. B. Rader (ed), “Turbata per aequora mundi”