Il Che

Lezione del 01/03/201

Lo sfruttamento minorile dei due mondi. Le fabbriche di Sesto San Giovanni. I giornali, le scarpe e i pugni di Kid Chocolate a L'Avana

Il lavoro minorile era, ed è ancora in tante parti del mondo, una piaga trasversale, che attraversa continenti e nazioni le più diverse. Per questo nel mio articolo parlo di Sesto San Giovanni, la mia città, e dell’Avana, dove ho vissuto a lungo. Agli inizi del ‘900, il lavoro minorile a Sesto, pesante, malsano, ingiusto, instradava in un percorso professionale che aveva un suo obiettivo perseguibile, diventare un operaio, un tecnico, un impiegato con un lavoro stabile, retribuito regolarmente. Ma all’Avana nemmeno questa prospettiva esisteva. Lo racconta la storia di Kid Chocolate, uno dei migliori pugili di tutti i tempi, che da bambino alternava il lavoro di lustrascarpe con quello di strillone

PEP and TasP Awareness among Italian MSM, PLWHA, and High-Risk Heterosexuals and Demographic, Behavioral, and Social Correlates

Post-exposure prophylaxis (PEP) has been proposed as a strategy to prevent the acquisition of HIV infection after certain high-risk exposures, and treatment as prevention (TasP) is also being advocated as a means to reduce sexual transmission of HIV. The aim of this study was to investigate the prevalence of PEP and TasP awareness and their demographic, behavioral, and social correlates in Italy. We conducted a cross-sectional survey of 1,028 high-risk heterosexual men and women, 1,874 non-HIV positive MSM (men who have sex with men), and 694 people living with HIV/AIDS (PLWHA). The majority of the participants was aware of PEP and unaware of TasP. MSM were less knowledgeable about PEP and TasP than were PLWHA and more knowledgeable about PEP and TasP than were high-risk heterosexual participants. The variables most consistently associated with PEP and TasP awareness were contact with HIV/AIDS organizations, HIV testing, and HIV stigma. A positive relationship between unprotected sexual intercourse and PEP and TasP awareness was found among high risk heterosexual participants, while this association was not significant among MSM and PLWHA. Because PEP and TasP are currently recommended, effective educational and dissemination strategies are needed to increase the level of knowledge about PEP and TasP

Proteomic snapshot of the EGF-induced ubiquitin network

In this work, the authors report the first proteome-wide analysis of EGF-regulated ubiquitination, revealing surprisingly pervasive growth factor-induced ubiquitination across a broad range of cellular systems and signaling pathways

Role of neuronal and inducible nitric oxide synthases in the guinea pig ileum myenteric plexus during in vitro ischemia and reperfusion

Background Intestinal ischemia and reperfusion (I/R) injury leads to abnormalities in motility, namely delay of transit, caused by damage to myenteric neurons. Alterations of the nitrergic transmission may occur in these conditions. This study investigated whether an in vitro I/R injury may affect nitric oxide (NO) production from the myenteric plexus of the guinea pig ileum and which NO synthase (NOS) isoform is involved. Methods The distribution of the neuronal (n) and inducible (i) NOS was determined by immunohistochemistry during 60 min of glucose/oxygen deprivation (in vitro ischemia) followed by 60 min of reperfusion. The protein and mRNA levels of nNOS and iNOS were investigated by Westernimmunoblotting and real time RT-PCR, respectively. NO levels were quantified as nitrite/nitrate. Key Results After in vitro I/R the proportion of nNOSexpressing neurons and protein levels remained unchanged. nNOS mRNA levels increased 60 min after inducing ischemia and in the following 5 min of reperfusion. iNOS-immunoreactive neurons, protein and mRNA levels were up-regulated during the whole I/R period. A significant increase of nitrite/nitrate levels was observed in the first 5 min after inducing I/R and was significantly reduced by Nx-propyl-L-arginine and 1400 W, selective inhibitors of nNOS and iNOS, respectively. Conclusions & Inferences Our data demonstrate that both iNOS and nNOS represent sources for NO overproduction in ileal myenteric plexus during I/R, although iNOS undergoes more consistent changes suggesting a more relevant role for this isoform in the alterations occurring in myenteric neurons following I/R

Impact of an abbreviated protocol for breast MRI in diagnostic accuracy

PURPOSE:We aimed to compare the diagnostic accuracy and interpretation time of an abbreviated protocol relative to the complete protocol of breast magnetic resonance imaging (MRI) with the use of breast imaging reporting and data system (BI-RADS). Between-reader and between-protocol variability for BI-RADS classification and influence of reader expertise on diagnostic accuracies were also evaluated.METHODS:We conducted a retrospective reader study in 90 women who underwent breast MRI: 30 benign examinations (graded as American College of Radiology [ACR] 1 or 2), 30 examinations graded as ACR 3 and 30 examinations requiring a histologic proof (graded as ACR 4 or 5). Two radiologists independently reviewed the protocols. The reference standard was 24 months of imaging follow-up (66.6%, n=60), percutaneous biopsy at the12th month imaging follow-up (5.5%, n=5), and breast surgery (27.9%, n=25). Analysis was done on a per-breast basis. There were 26 cancers in 168 breasts (15.1%)RESULTS:Interpretation time was higher for the complete protocol (mean difference: 84 s, 95% CI [67;101] for senior and 83 s, 95% CI [70;95] for junior reader; P < 0.001). The reliability of BI-RADS classification between both protocols was very good with intraclass correlation coefficient of 0.89 for junior reader and 0.98 for senior reader; the inter-reader reliability was 0.94 and 0.90 for the complete and abbreviated protocols, respectively. For senior reader, the abbreviated and complete protocols yielded 95.1% and 94.4% specificity and 100% sensitivity.CONCLUSION:Our data provide corroborating evidence that abbreviated protocols decrease interpretation time without compromising sensitivity or specificity. There was a high level of concordance between the abbreviated and complete protocols and between the two readers

Somatic genome editing with the RCAS-TVA-CRISPR-Cas9 system for precision tumor modeling

To accurately recapitulate the heterogeneity of human diseases, animal models require to recreate multiple complex genetic alterations. Here, we combine the RCAS-TVA system with the CRISPR-Cas9 genome editing tools for precise modeling of human tumors. We show that somatic deletion in neural stem cells of a variety of known tumor suppressor genes (Trp53, Cdkn2a, and Pten) leads to high-grade glioma formation. Moreover, by simultaneous delivery of pairs of guide RNAs we generate different gene fusions with oncogenic potential, either by chromosomal deletion (Bcan-Ntrk1) or by chromosomal translocation (Myb-Qk). Lastly, using homology-directed-repair, we also produce tumors carrying the homologous mutation to human BRAF V600E, frequently identified in a variety of tumors, including different types of gliomas. In summary, we have developed an extremely versatile mouse model for in vivo somatic genome editing, that will elicit the generation of more accurate cancer models particularly appropriate for pre-clinical testing.A.C.-G is recipient of a Severo-Ochoa PhD fellowship. C.M. and V.M. are recipients of a "La Caixa "PhD fellowship. We thank A.J. Schuhmacher for the initial assistance with the intracranial injections in adult mice and C.S. Clemente-Troncone for the technical support. We thank Carmen Blanco, David Olmeda, and Marisol Soengas for sharing reagents and Orlando Dominguez for the help with the design of the BRAF high- throughput sequencing. We sincerely thank Dr. José Luis Rodríguez Peralto (Hospital U. 12 de Octubre Madrid) for the BRAF V600 IHCs staining. This research was supported by funds from the Acción Estratégica en Salud Spanish National Research and Development Plan, Instituto de Salud Carlos III (ISCIII), cofounder by FEDER (ERDF) (PI14/01884) to S.R.-P., by a 017 Leonardo Grant for Researchers and Cultural Creators from the BBVA Foundation and a grant from the Seve Ballesteros Foundation to M.S.S

Combined chemical synthesis and tailored enzymatic elongation provide fully synthetic and conjugation-ready Neisseria meningitidis serogroup X vaccine antigens

Studies on the polymerization mode of Neisseria meningitidis serogroup X capsular polymerase CsxA recently identified a truncated construct that can be immobilized and used for length controlled on-column production of oligosaccharides. Here, we combined the use of a synthetic acceptor bearing an appendix for carrier protein conjugation and the on-column process to a novel chemo-enzymatic strategy. After protein coupling of the size optimized oligosaccharide produced by the one-pot elongation procedure, we obtained a more homogeneous glycoconjugate compared to the one previously described starting from the natural polysaccharide. Mice immunized with the conjugated fully synthetic oligomer elicited functional antibodies comparable to controls immunized with the current benchmark MenX glycoconjugates prepared from the natural capsule polymer or from fragments of it enzymatically elongated. This pathogen-free technology allows the fast total in vitro construction of predefined bacterial polysaccharide fragments. Compared to conventional synthetic protocols, the procedure is more expeditious and drastically reduces the number of purification steps to achieve the oligomers. Furthermore, the presence of a linker for conjugation in the synthetic acceptor minimizes manipulations on the enzymatically produced glycan prior to protein conjugation. This approach enriches the methods for fast construction of complex bacterial carbohydrates

Conformational and Immunogenicity Studies of the Shigella flexneri Serogroup 6 O-Antigen: The Effect of O-Acetylation.

The pathogenic bacterium Shigella is a leading cause of diarrheal disease and mortality, disproportionately affecting young children in low-income countries. The increasing prevalence of antibiotic resistance in Shigella necessitates an effective vaccine, for which the bacterial lipopolysaccharide O-antigen is the primary target. S. flexneri serotype 6 has been proposed as a multivalent vaccine component to ensure broad protection against Shigella. We have previously explored the conformations of S. flexneri O-antigens from serogroups Y, 2, 3, and 5 that share a common saccharide backbone (serotype Y). Here we consider serogroup 6, which is of particular interest because of an altered backbone repeat unit with non-stoichiometric O-acetylation, the antigenic and immunogenic importance of which have yet to be established. Our simulations show significant conformational changes in serogroup 6 relative to the serotype Y backbone. We further find that O-acetylation has little effect on conformation and hence may not be essential for the antigenicity of serotype 6. This is corroborated by an in vivo study in mice, using Generalized Modules for Membrane Antigens (GMMA) as O-antigen delivery systems, that shows that O-acetylation does not have an impact on the immune response elicited by the S. flexneri serotype 6 O-antigen