Nota preliminare sulle indagini archeologiche presso la grotta “Mora di Cavorso”

Si presentano i dati relativi allo scavo archeologico eseguito per il recupero di reperti umani segnalati nel 2003 presso la grotta Mora Cavorso a Jenne (Rm). Si tratta di varie centiania di ossa umane, fauna e materiale archeologico datati al Neolitico antico e probabilmente relativi a una serie di sepolture intenzionali sconvolte in antico

Anomalous last interglacial Tyrrhenian sea levels and Neanderthal settling at Guattari and Moscerini caves (central Italy)

We present a geological-stratigraphical study aimed to provide chronologic constraints to the sea-level markers occurring at two coastal caves of central Italy (Grotta Guattari and Grotta dei Moscerini) and to the Neanderthal frequentation of these caves, in the light of recent archaeological and geomorphological-geochronological studies suggesting similar sea levels during MIS 5.5 and MIS 5.3, and only few m below the Present during MIS 5.1 in this region. Based on the review of previous literature data, combined with new stratigraphic observations at Grotta Guattari and re-analysis of archive material including unpublished field notes from Grotta dei Moscerini, we reconstruct a plausible sea-level history accounting for the lithological and paleoenvironmental features of their sedimentary fillings. In particular, we outline the abundant occurrence of well-rounded pumice clasts within the sedimentary deposits of Moscerini Cave, attesting for the proximity to the beach where this pumice was gathered by wave action. Through the petrographic and geochemical analysis of this pumice we evidence provenance from Phlegraean Fields and Ischia Island volcanic districts, framing their chronology in the time span 118–40 ka, consistent with literature ESR-U/Th dates providing ages ranging 101 ± 5–74 ± 7 ka for the sedimentary filling of both Moscerini and Guattari caves

The double life of MULE in preeclamptic and IUGR placentae

The E3 ubiquitin ligase MULE (Mcl-1 Ubiquitin Ligases E3) targets myeloid cell leukemia factor 1 (Mcl-1) and tumor suppressor p53 for proteasomal degradation. Although Mcl-1 and p53 have been implicated in trophoblast cell death in preeclampsia (PE) and intrauterine growth restriction (IUGR), the mechanisms regulating their expression in the human placenta remains elusive. Herein, we investigated MULE's involvement in regulating Mcl-1 and p53 degradation during normal and abnormal (PE, IUGR) placental development. MULE expression peaked at 5–7 weeks of gestation, when oxygen tension is low and inversely correlated with that of Mcl-1 and p53. MULE efficiently bound to Mcl-1 and p53 and regulated their ubiquitination during placental development. Exposure of first trimester villous explants to 3% O2 resulted in elevated MULE expression compared with 20% O2. Low-oxygen-induced MULE expression in JEG3 choriocarcinoma cells was abolished by hypoxia-inducible factor (HIF)-1α siRNA. MULE was overexpressed in both PE and IUGR placentae. In PE, MULE preferentially targeted p53 for degradation, allowing accumulation of pro-apoptotic Mcl-1 isoforms. In IUGR, however, MULE targeted pro-survival Mcl-1, allowing p53 to accumulate and exert its apoptotic function. These data demonstrate that oxygen regulates Mcl-1 and p53 stability during placentation via HIF-1-controlled MULE expression. The different preferential targets of MULE in PE and IUGR placentae classify early-onset PE and IUGR as distinct molecular pathologies

Management of Toxicity Induced by Anti-EGFR Therapy in Metastatic Colorectal Cancer

Use of anti-epidermal growth factor receptor (anti-EGFR) agents has yielded significant advances in the treatment of patients with metastatic colorectal cancer. In fact these drugs, which include the monoclonal antibodies cetuximab and panitumumab, can be delivered both as a single agent and in combination with chemotherapy, achieving better survival and quality of life and in some cases also resectability of metastases. However, these agents can result in the development of toxicities that are usually different from those observed with chemotherapy alone. For the management of these adverse effects, proper knowledge is mandatory. Skin toxicity is the most frequent adverse effect. Other toxicities can be observed, such as hypomagnesemia, gastrointestinal toxicity, and thromboembolic events. Severe infusion reactions can be life-threatening. For these reasons a review of anti-EGFR-drug-related toxicity is useful for clinical practice