Riflessioni sulla fabbrica di San Simpliciano e le sue trasformazioni medievali a settantacinque anni dalla riscoperta

Il contributo ripercorre la scoperta delle fasi costruttive taroantiche e medievali ella basilica di San Simpliciano Milano alla luce delle ultime indagini condotte sul monumento

PD/1-PD-Ls Checkpoint: Insight on the Potential Role of NK Cells

The identification of inhibitory NK cell receptors specific for HLA-I molecules (KIRs and NKG2A) provided the molecular basis for clarifying the mechanism by which NK cells kill transformed cells while sparing normal cells. The direct interactions between inhibitory NK cell receptors and their HLA-I ligands enable NK cells to distinguish healthy from transformed cells, which frequently show an altered expression of HLA-I molecules. Indeed, NK cells can kill cancer cells that have lost, or under express, HLA-I molecules, but not cells maintaining their expression. In this last case, it is possible to use anti-KIR or anti-NKG2A monoclonal antibodies to block the inhibitory signals generated by these receptors and to restore the anti-tumor NK cell activity. These treatments fall within the context of the new immunotherapeutic strategies known as "immune checkpoint blockade." These antibodies are currently used in clinical trials in the treatment of both hematological and solid tumors. However, a more complex scenario has recently emerged. For example, NK cells can also express additional immune checkpoints, including PD-1, that was originally described on T lymphocytes, and whose ligands (PD-Ls) are usually overexpressed on tumor cells. Thus, it appears that the activation of NK cells and their potentially harmful effector functions are under the control of different immune checkpoints and their simultaneous expression could provide additional levels of suppression to anti-tumor NK cell responses. This review is focused on PD-1 immune checkpoint in NK cells, its potential role in immunosuppression, and the therapeutic strategies to recover NK cell cytotoxicity and anti-tumor effect

Shiga toxin-producing Escherichia coli O157, O26 and O111 in cattle faeces and hides in Italy

Introduction: Ruminants are regarded as the natural reservoir for Shiga toxin-producing Escherichia coli (STEC), especially of serogroup O157. Materials and methods: During 2011 and 2012, 320 samples (160 faecal samples from the rectum and 160 hide samples from the brisket area) were collected from 160 cattle at slaughter in Northern Italy during warm months (May to October). Cattle were reared in different farms and their age at slaughter ranged between nine months and 15 years, most of them being culled cattle (median age: six years; average age: 4.6 years). Samples were tested by immunomagneticseparation technique for E coli O157 and O26 and by a screening PCR for stx genes followed by cultural detection of STEC. The virulence genes stx1, stx2, eae, and e-hlyA were detected and among stx2-positive isolates the presence of the stx2a and stx2c variants was investigated. Results: Twenty-one of 160 cattle (13.1 per cent; 95 per cent CI 8.3 to 19.4 per cent) were found to be faecal carriers of STEC. STEC O157 was found in 10 (6.3 per cent) samples, STEC O26 in six (3.8 per cent) and STEC O111 in one (0.6 per cent). Four isolates (2.5 per cent) were O not determined (OND). Six out of 160 (3.8 per cent; 95 per cent CI 1.4 to 8.0 per cent) hide samples were positive for STEC; four hides (2.5 per cent) were contaminated by STEC O157 and two (1.3 per cent) by STEC O26. In three cattle (1.9 per cent) STEC from both faeces and hides were detected. Among STEC O157, 87.5 per cent of them carried the stx2c gene and 12.5 per cent carried both stx1 and stx2c genes. No O157 isolate harboured stx2a variant. STEC O26 and O111 carried the stx1 gene only. One OND strain carried both the stx2a and stx2c genes. Conclusions: This study shows that STEC O157 from cattle can harbour the stx2c variant, which is associated with haemolytic uraemic syndrome in humans, and that cattle hides may be a source of human pathogenic STEC O157 and O26 in the slaughterhouse environment

Harnessing NK Cells for Cancer Treatment

In the last years, natural killer (NK) cell-based immunotherapy has emerged as a promising therapeutic approach for solid tumors and hematological malignancies. NK cells are innate lymphocytes with an array of functional competences, including anti-cancer, anti-viral, and anti-graft-vs.-host disease potential. The intriguing idea of harnessing such potent innate immune system effectors for cancer treatment led to the development of clinical trials based on the adoptive therapy of NK cells or on the use of monoclonal antibodies targeting the main NK cell immune checkpoints. Indeed, checkpoint immunotherapy that targets inhibitory receptors of T cells, reversing their functional blocking, marked a breakthrough in anticancer therapy, opening new approaches for cancer immunotherapy and resulted in extensive research on immune checkpoints. However, the clinical efficacy of T cell-based immunotherapy presents a series of limitations, including the inability of T cells to recognize and kill HLA-Ineg tumor cells. For these reasons, new strategies for cancer immunotherapy are now focusing on NK cells. Blockade with NK cell checkpoint inhibitors that reverse their functional block may overcome the limitations of T cell-based immunotherapy, mainly against HLA-Ineg tumor targets. Here, we discuss recent anti-tumor approaches based on mAb-mediated blocking of immune checkpoints (either restricted to NK cells or shared with T cells), used either as a single agent or in combination with other compounds, that have demonstrated promising clinical responses in both solid tumors and hematological malignancie

"Twisted and rolled body hairs": an ultrastructural study by means of scanning electron microscopy.

No Abstract availabl

Riflessioni sulla fabbrica di San Simpliciano e le sue trasformazioni medievali a settantacinque anni dalla riscoperta

Il contributo ripercorre la scoperta delle fasi costruttive taroantiche e medievali ella basilica di San Simpliciano Milano alla luce delle ultime indagini condotte sul monumento

Trame del tempo. Per le Scuole superiori. Vol. 1

In Trame del tempo, la storia raccontata diventa materia viva e coinvolgente, si anima di voci, immagini, grandi protagonisti e persone comuni. Il racconto si fa anche laboratorio dello storico attraverso la stretta integrazione di documenti, storiografia, immagini e carte nei paragrafi (Materiali), accogliendo tutte le novità della storiografia più recente e senza schede e apparati paratestuali che lo interrompano. Alle studentesse e agli studenti viene così mostrato come “fare storia” significhi da un lato narrare storie, e dall'altro ragionare costantemente sulla loro fondatezza, e sulla solidità delle tracce che ci portano a raccontarle. Ogni Capitolo si apre con una Chiave di lettura in cui l’autore o l’autrice offre un punto di vista su come leggere le pagine che seguono. Documenti, storiografia, fonti iconografiche, carte (Materiali) sono inseriti nella narrazione storica e non confinati in apparati di corredo. A fine capitolo: cronologia e sintesi lineare degli eventi e dei processi fondamentali (Conoscenze di base), e batterie di attività (Per l’apprendimento) che vanno dalla memorizzazione alla analisi dei Materiali (fonti, storiografia, ecc.) del capitolo. Per ogni Unità: Nel Laboratorio dello storico su storiografia, fonti, storia e immaginario (letteratura, arte, film, cultura pop); Laboratorio delle competenze su prove scritte e orale dell’Esame di Stato. In ciascun volume: Per diventare cittadin@, ampie schede di Educazione civica. La progettazione dei contenuti digitali integrativi – videolezioni d’autore e flipped classroom per ogni capitolo, Lavorare sulla fonte, La storia online, La storia in scena, mappe concettuali, Lezioni EAS, e un ricco repertorio di fonti e storiografia aggiuntive – è stata affidata a una docente esperta in didattica digitale e media literacy, Enrica Bricchetto. La Guida alle lezioni e didattica digitale, riservata ai docenti, propone per ogni volume programmazioni, verifiche, soluzioni, indicazioni per la progettazione del PCTO e le sezioni Le lezioni: un percorso guidato. Con strumenti per la didattica inclusiva, in cui per ogni capitolo del manuale si suggeriscono possibilità di articolazione delle lezioni a partire da materiali documentari incorporati nel testo o disponibili online, Obiettivi didattici minimi e strumenti inclusivi