IL28B expression depends on a novel TT/-G polymorphism which improves HCV clearance prediction

Approximately 3% of the world population is chronically infected with the hepatitis C virus (HCV), with potential development of cirrhosis and hepatocellular carcinoma. Despite the availability of new antiviral agents, treatment remains suboptimal. Genome-wide association studies (GWAS) identified rs12979860, a polymorphism nearby IL28B, as an important predictor of HCV clearance. We report the identification of a novel TT/-G polymorphism in the CpG region upstream of IL28B, which is a better predictor of HCV clearance than rs12979860. By using peripheral blood mononuclear cells (PBMCs) from individuals carrying different allelic combinations of the TT/-G and rs12979860 polymorphisms, we show that induction of IL28B and IFN-γ–inducible protein 10 (IP-10) mRNA relies on TT/-G, but not rs12979860, making TT/-G the only functional variant identified so far. This novel step in understanding the genetic regulation of IL28B may have important implications for clinical practice, as the use of TT/G genotyping instead of rs12979860 would improve patient management.

Risposta a dell' ... Vincenzo Berni Degli antonj ... ai dubbj eccitati dal ... avvocato Francesco Gualandi sulle osservazioni al voto consultivo del ... avvocato Giovanni Vicini nella quistione di simultanae consuccessione di Cristiani e di Ebrei alle intestata eredità di un loro congiunto Cristiano

Vincenzo Berni Degli Antonj

A novel animal model for external anal sphincter insufficiency

Abstract PURPOSE: Reliable animal models are essential to evaluate future therapeutic options like cell-based therapies for external anal sphincter insufficiency. The goal of our study was to describe the most reliable model for external sphincter muscle insufficiency by comparing three different methods to create sphincter muscle damage. METHODS: In an experimental animal study, female Lewis rats (200-250 g) were randomly assigned to three treatment groups (n = 5, each group). The external sphincter muscle was weakened in the left dorsal quadrant by microsurgical excision, cryosurgery, or electrocoagulation by diathermy. Functional evaluation included in vivo measurements of resting pressure, spontaneous muscle contraction, and contraction in response to electrical stimulation of the afferent nerve at baseline and at 2, 4, and 6 weeks after sphincter injury. Masson's trichrome staining and immunofluorescence for skeletal muscle markers was performed for morphological analysis. RESULTS: Peak contraction after electrical stimulation was significantly decreased after sphincter injury in all groups. Contraction forces recovered partially after cryosurgery and electrocoagulation but not after microsurgical excision. Morphological analysis revealed an incomplete destruction of the external sphincter muscle in the cryosurgery and electrocoagulation groups compared to the microsurgery group. CONCLUSIONS: For the first time, three different models of external sphincter muscle insufficiency were directly compared. The animal model using microsurgical sphincter destruction offers the highest level of consistency regarding tissue damage and sphincter insufficiency, and therefore represents the most reliable model to evaluate future therapeutic options. In addition, this study represents a novel model to specifically test the external sphincter muscle function.

Dynamics of a Tularemia Outbreak in a Closely Monitored Free-Roaming Population of Wild House Mice.

Infectious disease outbreaks can be devastating because of their sudden occurrence, as well as the complexity of monitoring and controlling them. Outbreaks in wildlife are even more challenging to observe and describe, especially when small animals or secretive species are involved. Modeling such infectious disease events is relevant to investigating their dynamics and is critical for decision makers to accomplish outbreak management. Tularemia, caused by the bacterium Francisella tularensis, is a potentially lethal zoonosis. Of the few animal outbreaks that have been reported in the literature, only those affecting zoo animals have been closely monitored. Here, we report the first estimation of the basic reproduction number R0 of an outbreak in wildlife caused by F. tularensis using quantitative modeling based on a susceptible-infected-recovered framework. We applied that model to data collected during an extensive investigation of an outbreak of tularemia caused by F. tularensis subsp. holarctica (also designated as type B) in a closely monitored, free-roaming house mouse (Mus musculus domesticus) population in Switzerland. Based on our model and assumptions, the best estimated basic reproduction number R0 of the current outbreak is 1.33. Our results suggest that tularemia can cause severe outbreaks in small rodents. We also concluded that the outbreak self-exhausted in approximately three months without administrating antibiotics.

Zur Geschichte der Juden in Spanien von 1385

Moritz Levin

Na 50 Nachlass Arthur Schopenhauer - 'Schopenhauer-Archiv', 1432 - Philosophari (Excerpte)

Bereitgestellt mit freundlicher Unterstützung der Staatsbibliothek zu Berlin - Preußischer Kulturbesitz

Fürtrefflicher Ritter-Kampf, Der zweyen Neapolitanischen Fürsten D. Francesco Carafa de Noja und D. Guilio Antonio Aquaviva de Aragona : am 5., 15. Novemb. 1673

Bibliograph. Nachweis: VD 17 1:620759R; Drugulin 2845

Francesco Graziani, Hüftbild

Signatur des Originals: S 36/F00604

Elsa Kment als Mona Fiordalisa, Herbert Hesse als Francesco del Giocondo, Szenenfoto, Doppelbildnis, in: Max von Schillings: Mona Lisa, Frankfurt a. M.

Signatur des Originals: S 36/F08965

Giuseppe Verdi, Francesco Tamagno, Doppelbildnis

Signatur des Originals: S 36/F10036

Francesco Tamagno, Brustbild

Signatur des Originals: S 36/F10037

Giuseppe Verdi, Francesco Tamagno, Doppelbildnis

Signatur des Originals: S 36/F10117

Francesco Bernardi, Brustbild

Signatur des Originals: S 36/G00007

Francesco Benucci, Brustbild

Signatur des Originals: S 36/G00420