Lack of cathelicidin processing in Papillon-Lefèvre syndrome patients reveals essential role of LL-37 in periodontal homeostasis.

BACKGROUND Loss-of-function point mutations in the cathepsin C gene are the underlying genetic event in patients with Papillon-Lefèvre syndrome (PLS). PLS neutrophils lack serine protease activity essential for cathelicidin LL-37 generation from hCAP18 precursor. AIM We hypothesized that a local deficiency of LL-37 in the infected periodontium is mainly responsible for one of the clinical hallmark of PLS: severe periodontitis already in early childhood. METHODS To confirm this effect, we compared the level of neutrophil-derived enzymes and antimicrobial peptides in gingival crevicular fluid (GCF) and saliva from PLS, aggressive and chronic periodontitis patients. RESULTS Although neutrophil numbers in GCF were present at the same level in all periodontitis groups, LL-37 was totally absent in GCF from PLS patients despite the large amounts of its precursor, hCAP18. The absence of LL-37 in PLS patients coincided with the deficiency of both cathepsin C and protease 3 activities. The presence of other neutrophilic anti-microbial peptides in GCF from PLS patients, such as alpha-defensins, were comparable to that found in chronic periodontitis. In PLS microbial analysis revealed a high prevalence of Aggregatibacter actinomycetemcomitans infection. Most strains were susceptible to killing by LL-37. CONCLUSIONS Collectively, these findings imply that the lack of protease 3 activation by dysfunctional cathepsin C in PLS patients leads to the deficit of antimicrobial and immunomodulatory functions of LL-37 in the gingiva, allowing for infection with A. actinomycetemcomitans and the development of severe periodontal disease.

ll "Pasquillus extaticus" di Celio Secondo Curione: eresia, censura, tradizione a stampa e manoscritta del testo

The essay examines the print and manuscript traditions of the "Pasquillus extaticus" by Celio Secondo Curione with a particular focus on their relation with censorship. At first, the essay investigates into the redactional evolution and into the editorial history of the dialogue and of its vernacular versions, e.g. the relation between some editions of the "Pasquillus extaticus" and of the "Pasquino in estasi" (which appeared anonymously and without typographical information) and the provisions of political and ecclesiastical censorship in the 16th century. Finally, analysing the manuscript tradition, the essay discusses Carlos Gilly’s identification of «Coelii Secundi Pasquillus, emendatus impress[us]», registered in the inventory of the private library of the Basel typographer Johannes Oporinus, with the copy preserved at the Herzog August Bibibliothek Wolfenbüttel [hab: p 1811. 8º Helmst. (1)]). The author refutes Gilly’s hypothetical attribution to Curione’s handwriting of the many marginalia present in this copy.

Impact de la fabrication de charbon de bois sur la production et la disponibilité fourragère de pâturage en zone subaride, cas de la commune de Soalara-Sud, Toliara ll: Rapport final

Ce projet a pour objectif de (1) décrire la filière charbon dans un terroir de la commune de Soalara, (2) d’identifier les effets des activités de fabrication de charbon de bois sur la végétation des pâturages qui est un fourré épineux et (3) d’estimer la quantité maximale de charbon pouvant être produite sans causer sa dégradation irréversible. Pour ce faire, des enquêtes auprès de la population locale et des relevés écologiques ont été entrepris. La majorité des ménages enquêtés (>80% ; N=56) pratiquent la fabrication de charbon de bois. Environ 41 000 sacs de charbons ont été produits dans le terroir en 2009. L’impact socio-économique de la filière charbon est positif puisqu’elle génère des revenus importants pour ses agents (producteur, transporteur et collecteur). Par contre, l’impact écologique est plutôt négatif puisque les activités charbonnières contribuent à réduire la densité d’arbres et d’arbustes de la végétation des fourrés épineux et sa richesse spécifique même si elles n’affectent pas trop sa disponibilité fourragère. De plus, la quantité de charbon produite (environ 820 t en 2009) dépasse la productivité de la végétation, estimée à 218 t.an-1. Par conséquent, une dégradation du site de production actuel, se traduisant par la disparition des espèces charbonnières, arriverait dans 17 ans au plus tard, si le rythme de production actuel continue. Des mesures de réduction des pressions sur la végétation (professionnalisation des éleveurs, amélioration des rendements de carbonisation et réglementation et contrôle plus strict de la filière charbon) et d’augmentation de sa production et productivité (restauration) doivent être prises pour éviter cette dégradation irréversible qui à terme pourrait être dommageable à l’élevage de petits ruminants même si ce n’est pas encore le cas actuellement.

Vitamin D represses rhinovirus replication in cystic fibrosis cells by inducing LL-37.

Vitamin D has immunomodulatory properties in the defence against pathogens. Its insufficiency is a widespread feature of cystic fibrosis (CF) patients, which are repeatedly suffering from rhinovirus (RV)-induced pulmonary exacerbations.To investigate whether vitamin D has antiviral activity, primary bronchial epithelial cells from CF children were pre-treated with vitamin D and infected with RV16. Antiviral and anti-inflammatory activity of vitamin D was assessed. RV and LL-37 levels were measured in bronchoalveolar lavage (BAL) of CF children infected with RV.Vitamin D reduced RV16 load in a dose-dependent manner in CF cells (10(-7 )M, p<0.01). The antiviral response mediated by interferons remained unchanged by vitamin D in CF cells. Vitamin D did not exert anti-inflammatory properties in RV-infected CF cells. Vitamin D increased the expression of the antimicrobial peptide LL-37 up to 17.4-fold (p<0.05). Addition of exogenous LL-37 decreased viral replication by 4.4-fold in CF cells (p<0.05). An inverse correlation between viral load and LL-37 levels in CF BAL (r=-0.48, p<0.05) was observed.RV replication in primary CF bronchial cells was reduced by vitamin D through the induction of LL-37. Clinical studies are needed to determine the importance of an adequate control of vitamin D for prevention of virus-induced pulmonary CF exacerbations.

Life of Samuel Johnson, LL.D. comprehending an account of his studies, and numerous works in chronological order : with his correspondence and conversations

by James Boswell ; with copious notes and biograph. ill. by Malone

Marie Jae͏̈ll, Ganzfigurbildnis

Signatur des Originals: S 36/F01996

Defensio Joannis Reuchlin Phorcensis LL. Doctoris Contra Calvmniatores Svos Colonienses

Johannes Reuchlin

Report on the Hydroida : collected during the exploration of the Gulf Stream by L. F. de Pourtalès, assistant United States Coast Survey / by Geo. J. Allman, M.D., LL.D., ...

v.5:no.2 (1877)

Hādhihī al-risālah Naṣīḥat al-ikhwān fī ṣawm Rajab wa-Shaʻbān wa-Ramaḍān / taʼlīf al-Shaykh al-ʻĀlim al-ʻĀllāmah al-ʻUmdah al-Fahhāmah al-Shaykh Ismāʻīl al-Jarrāḥī al-ʻAjlūnī : manuscript, undated

Holograph copy.

Del riparo de' pennelli alle rive del Po di Cremona : a sua eccellenza il signor marchese don Angiolo Luigi Maraviglia Mantegazza, consigliere intimo attuale di stato delle Ll. maestáa imperiali, e presidente della regia camera ec.

Acquisition made accessible thanks to a 2015-2017 grant from the Council on Libraries and Information Resources.

In memoriam. Josiah Clark, LL.D., principal of Williston Seminary 1849-1863. : Obiit [sic] May 30, 1878. /

"Published by the Trustees of Williston Seminary, for gratuitous distribution among the Alumni, and other friends of Williston Seminary"--T.p. verso.

A memorial discourse of Nathaniel F. Moore, LL.D. : sometime president of Columbia College, New York, delivered at the request of the alumni, January 14, 1874, in the college chapel /

Published by direction of the alumni and of the board of trustees.