Antagomir-17-5p Abolishes the Growth of Therapy-Resistant Neuroblastoma through p21 and BIM

We identified a key oncogenic pathway underlying neuroblastoma progression: specifically, MYCN, expressed at elevated level, transactivates the miRNA 17-5p-92 cluster, which inhibits p21 and BIM translation by interaction with their mRNA 3′ UTRs. Overexpression of miRNA 17-5p-92 cluster in MYCN-not-amplified neuroblastoma cells strongly augments their in vitro and in vivo tumorigenesis. In vitro or in vivo treatment with antagomir-17-5p abolishes the growth of MYCN-amplified and therapy-resistant neuroblastoma through p21 and BIM upmodulation, leading to cell cycling blockade and activation of apoptosis, respectively. In primary neuroblastoma, the majority of cases show a rise of miR-17-5p level leading to p21 downmodulation, which is particularly severe in patients with MYCN amplification and poor prognosis. Altogether, our studies demonstrate for the first time that antagomir treatment can abolish tumor growth in vivo, specifically in therapy-resistant neuroblastoma

Earthquake damage assessment of masonry churches: proposal for rapid and detailed forms and derivation of empirical vulnerability curves

The post-earthquake damage assessment represents the first step after an emergency to support not only the safety of people, but also the preservation of buildings through the realization of prompt and effective provisional interventions. The issue is of particular relevance in case of monumental assets such as churches that are the focus of the paper. In Italy, since 1997 the post-earthquake damage assessment of churches has been carried out using a specific form, which was formally approved in 2001 by the Italian Civil Protection. Being the most advanced tool available in the literature within this specific field, the Italian form has been widely used also internationally. It follows the approach based on the decomposition of the church into macroelements. Although the latter has found wide confirmation through the interpretation of real damage, some critical issues were raised in relation to the versatility of the form and the reliability of the damage index that the approach provides. The post-earthquake damage assessment of 48 unreinforced masonry churches located in New Zealand, hit by the Canterbury earthquake sequence 2010\u20132011, represented an unprecedented opportunity, at international level, to investigate and to address the aforementioned issues. Starting from some weaknesses of the actual form, a new proposal (named CAF-D) for the damage assessment of unreinforced masonry churches has been developed and presented in the paper. The new form is still based on the macroelement approach, but it considers, in a separate way, the macroelements and the seismic damage modes they might develop, thus overcoming the limitation of the fixed number of damage mechanisms identified a priori by the current Italian form. The more reliable damage assessment approach that such form aims to achieve is the prelude to the development of a specific vulnerability model, derived by combining an empirical and an expert elicitation approach. A specific vulnerability model developed for New Zealand churches, derived by implementing the proposed CAF-D form and the related damage assessment procedure, is presented in the last part of the paper

Le Peuple : organe quotidien du syndicalisme

16 mars 19361936/03/16 (A16,N5535)-1936/03/16

CT043, a Protective Antigen That Induces a CD4+ Th1 Response during Chlamydia trachomatis Infection in Mice and Humans▿

Despite several decades of intensive studies, no vaccines against Chlamydia trachomatis, an intracellular pathogen causing serious ocular and urogenital diseases, are available yet. Infection-induced immunity in both animal models and humans strongly supports the notion that for a vaccine to be effective a strong CD4+ Th1 immune response should be induced. In the course of our vaccine screening program based on the selection of chlamydial proteins eliciting cell-mediated immunity, we have found that CT043, a protein annotated as hypothetical, induces CD4+ Th1 cells both in chlamydia-infected mice and in human patients with diagnosed C. trachomatis genital infection. DNA priming/protein boost immunization with CT043 results in a 2.6-log inclusion-forming unit reduction in the murine lung infection model. Sequence analysis of CT043 from C. trachomatis human isolates belonging to the most representative genital serovars revealed a high degree of conservation, suggesting that this antigen could provide cross-serotype protection. Therefore, CT043 is a promising vaccine candidate against C. trachomatis infection