Central tolerance shapes the neutralizing B cell repertoire against a persisting virus in its natural host

Viral mimicry of host cell structures has been postulated to curtail the B cell receptor (BCR) repertoire against persisting viruses through tolerance mechanisms. This concept awaits, however, experimental testing in a setting of natural virus–host relationship. We engineered mouse models expressing a monoclonal BCR specific for the envelope glycoprotein of lymphocytic choriomeningitis virus (LCMV), a naturally persisting mouse pathogen. When the heavy chain of the LCMV-neutralizing antibody KL25 was paired with its unmutated ancestor light chain, most B cells underwent receptor editing, a behavior reminiscent of autoreactive clones. In contrast, monoclonal B cells expressing the same heavy chain in conjunction with the hypermutated KL25 light chain did not undergo receptor editing but exhibited low levels of surface IgM, suggesting that light chain hypermutation had lessened KL25 autoreactivity. Upon viral challenge, these IgM $^{low}$ cells were not anergic but up-regulated IgM, participated in germinal center reactions, produced antiviral antibodies, and underwent immunoglobulin class switch as well as further affinity maturation. These studies on a persisting virus in its natural host species suggest that central tolerance mechanisms prune the protective antiviral B cell repertoire

Insegnare l’Europa. Concetti e rappresentazioni nei libri di testo europei

Il volume presenta i risultati di una ricerca comparata che ha analizzato i manuali scolastici utilizzati oggi nei diversi paesi europei per verificare quale spazio abbia in essi la trattazione dell’Europa, quali valori e concetti vengano presentati come caratterizzanti la civiltà europea, e in quali modi l’attenzione alle appartenenze nazionali venga coniugata con la nuova centralità dell’Europa.- Indice #5- Introduzione Nazioni ed Europa nell’educazione scolastica: come vediamo noi stessi e gli “altri”?, Falk Pingel #13- Insegnare la singolarità dell’Europa, Charles Olivier Carbonell #75- Tradizione religiosa e identità nazionale nell’Europa sudorientale, Răzvan Theodorescu #103- Cittadino, europeo e cosmopolita: scopi e compiti dell’educazione civica, Alistair Ross #119- Diversi modi di vedere l’integrazione europea, Juan Díez Medrano #153- Tendenze attuali nei manuali spagnoli di storia e di geografia dell’educazione secondaria obbligatoria, Rafael Valls #173- L’Europa nei programmi e nei manuali scolastici francesi: verso una nuova comunità immaginaria europea?, Hélène Baeyens #189- L’Europa del Novecento: un’analisi dei manuali di storia della scuola media italiana degli anni Novanta, Luigi Cajani #141- “Una nuova cultura capace di superare nazionalismi e separatismi”. Esempi da libri di educazione civica italiani, Olga Bombardelli #239- L’Europa nei libri di testo di storia del Regno Unito: insegnamento e apprendimento, Keith Crawford #265- L’Europa nei testi di geografia inglesi, John Hopkin #295- “Un lento avvicinamento all’Europa”: la dimensione europea nei testi britannici di storia contemporanea, Mark Engel #319- L’Europa si sta aprendo al resto del mondo? I cambiamenti avvenuti nella rappresentazione dell’Europa nei testi scolastici della Germania dopo la riunificazione (Wende) del 1989/90, Rolf Westheider #329- Visioni del mondo legate alla geografia: l’Europa vista dagli studenti della Germania, Armin Hüttermann #353- Cittadini della Germania e dell’Ue. La rappresentazione dell’Europa nei manuali scolastici tedeschi di educazione politica, K. Peter Fritzsche #375- L’Europa nei manuali greci di educazione civica, Despina Karakatsani #395- Dalla rivoluzione mondiale al dominio degli ambienti culturali? La rappresentazione dell’Europa nei testi scolastici russi di “storia mondiale”, Michail A. Bojcov #417- Alla ricerca di un cammino verso l’Europa: la dimensione europea nei testi di storia del XX secolo della Russia, Vera Kaplan #441- L’immagine dell’Europa nei libri di testo della Romania, Mirela Luminiţa Murgescu #473- L’”altra” entità politica esterna e le immagini dell’Europa nei manuali di storia moderna della Bulgaria successivi al 1917, Snezhana Dimitrova #501- La storia europea all’università di Belgrado: momenti concettuali della sua rappresentazione, Milan Ristović #521- Ricerca storica e redazione dei libri di testo nelle entità statali nate dalla Jugoslavia socialista, Neven Budak #535- Tra euforia, moderazione e isolamento: l’Europa nei testi scolastici di storia delle repubbliche della ex Jugoslavia, Heike Karge #551- Prospettive sull’educazione ai diritti dell’uomo nella Repubblica serba, Aleksandra Petrović #59

Immunology of persistent viral infection

Perturbed B cell responses and late formation of neutralizing antibodies are hallmarks of chronic infections but the mechanisms underlying the dysfunctional humoral responses remain poorly defined. We used adoptive transfer of monoclonal anti-viral B cells (KL25) in the context of chronic lymphocytic choriomeningitis virus (LCMV) infection in mice and we observed late clonal deletion of the KL25 cells. This process was governed by the binding affinity of the KL25 B cell receptor (BCR) to its target, the viral glycoprotein (GP), and the persistence of the antigen. We found that the loss of the KL25 B cells was independent of IFN-I inflammation, and it was the result of terminal differentiation into short-lived antibody secreting cells (ASCs). In a striking difference to antiviral T cells, long-term viremia did not result in a significantly altered transcriptional program in the LCMV- specific B cells compartment. The late deletion of high-affinity B cells in chronic infection may explain the delayed neutralizing antibody response to persistent pathogens. Strategies to counter B cell clonal deletion should help us improve humoral immunity against chronic infectious diseases

Dual-Energy CT Iodine Uptake of Head and Neck: Definition of Reference Values in a Big Data Cohort

Background: Despite a considerable amount of literature on dual-energy CT (DECT) iodine uptake of the head and neck, the physiologic iodine uptake of this region has not been defined yet. This study aims to establish reference values for the iodine uptake of healthy organs to facilitate clinical application. Methods: Consecutive venous DECT scans of the head and neck were reviewed, and unremarkable exams were included (n = 617). A total of 35 region of interest measurements were performed in 16 anatomical regions. Iodine uptake was compared among different organs/tissues and subgroup analysis was performed (male (n = 403) vs. female (n = 214); young (n = 207) vs. middle-aged (n = 206) vs. old (n = 204); and normal weight (n = 314) vs. overweight (n = 196) vs. obese (n = 107)). Results: Overall mean iodine uptake values ranged between 0.5 and 9.4 mg/mL. Women showed higher iodine concentrations in the cervical vessels and higher uptake for the parotid gland, masseter muscle, submandibular glands, sublingual glands, palatine tonsils, tongue body, thyroid gland, and the sternocleidomastoid muscle than men (p ≤ 0.04). With increasing age, intravascular iodine concentrations increased as well as iodine uptake for cerebellum and thyroid gland, while values for the tongue and palatine tonsils were lower compared to younger subjects (p ≤ 0.03). Iodine concentrations for parotid glands and sternocleidomastoid muscles decreased with a higher BMI (p ≤ 0.004), while normal-weighted patients showed higher iodine values inside the jugular veins, other cervical glands, and tonsils versus patients with a higher BMI (p ≤ 0.04). Conclusion: physiologic iodine uptake values of cervical organs and tissues show gender-, age-, and BMI-related differences, which should be considered in the clinical routine of head and neck DECT

Diagnosis of an Acute Anterior Wall Infarction in Dual-Energy CT

Due to its high morbidity and mortality, myocardial infarction is the leading cause of death worldwide. Against this background, rapid diagnosis is of immense importance. Especially in case of an atypical course, the correct diagnosis may be delayed and thus lead to increased mortality rates. In this report, we present a complex case of acute coronary syndrome. A triple-rule-out CT examination was performed in dual-energy CT (DECT) mode. While pulmonary artery embolism and aortic dissection could be ruled out with conventional CT series, the presence of anterior wall infarction was only detectable on DECT reconstructions. Subsequently, adequate and rapid therapy was then initiated leading to survival of the patient

Central tolerance shapes the neutralizing B cell repertoire against a persisting virus in its natural host

Viral mimicry of host cell structures has been postulated to curtail the B cell receptor (BCR) repertoire against persisting viruses through tolerance mechanisms. This concept awaits, however, experimental testing in a setting of natural virus-host relationship. We engineered mouse models expressing a monoclonal BCR specific for the envelope glycoprotein of lymphocytic choriomeningitis virus (LCMV), a naturally persisting mouse pathogen. When the heavy chain of the LCMV-neutralizing antibody KL25 was paired with its unmutated ancestor light chain, most B cells underwent receptor editing, a behavior reminiscent of autoreactive clones. In contrast, monoclonal B cells expressing the same heavy chain in conjunction with the hypermutated KL25 light chain did not undergo receptor editing but exhibited low levels of surface IgM, suggesting that light chain hypermutation had lessened KL25 autoreactivity. Upon viral challenge, these IgMlow cells were not anergic but up-regulated IgM, participated in germinal center reactions, produced antiviral antibodies, and underwent immunoglobulin class switch as well as further affinity maturation. These studies on a persisting virus in its natural host species suggest that central tolerance mechanisms prune the protective antiviral B cell repertoire.ISSN:0027-8424ISSN:1091-649

Студентска научна конференция "Здравеопазването-днес и утре", 22 Май 2013, Варна

Варненски медицински форум (Varna Medical Forum) V. 2, Suppl 4 (2013

Mass Reproducibility and Replicability: A New Hope

This study pushes our understanding of research reliability by reproducing and replicating claims from 110 papers in leading economic and political science journals. The analysis involves computational reproducibility checks and robustness assessments. It reveals several patterns. First, we uncover a high rate of fully computationally reproducible results (over 85%). Second, excluding minor issues like missing packages or broken pathways, we uncover coding errors for about 25% of studies, with some studies containing multiple errors. Third, we test the robustness of the results to 5,511 re-analyses. We find a robustness reproducibility of about 70%. Robustness reproducibility rates are relatively higher for re-analyses that introduce new data and lower for re-analyses that change the sample or the definition of the dependent variable. Fourth, 52% of re-analysis effect size estimates are smaller than the original published estimates and the average statistical significance of a re-analysis is 77% of the original. Lastly, we rely on six teams of researchers working independently to answer eight additional research questions on the determinants of robustness reproducibility. Most teams find a negative relationship between replicators' experience and reproducibility, while finding no relationship between reproducibility and the provision of intermediate or even raw data combined with the necessary cleaning codes