Counteraction of HCV-induced oxidative stress concurs to establish chronic infection in liver cell cultures

Hepatitis C virus (HCV) is a blood-borne pathogen causing acute and chronic hepatitis. A significant number of people chronically infected with HCV develop cirrhosis and/or liver cancer. The pathophysiologic mechanisms of hepatocyte damage associated with chronic HCV infection are not fully understood yet, mainly due to the lack of an in vitro system able to recapitulate the stages of infection in vivo. Several studies underline that HCV virus replication depends on redox-sensitive cellular pathways; in addition, it is known that virus itself induces alterations of the cellular redox state. However, the exact interplay between HCV replication and oxidative stress has not been elucidated. In particular, the role of reduced glutathione (GSH) in HCV replication and infection is still not clear. We set up an in vitro system, based on low m.o.i. of Huh7.5 cell line with a HCV infectious clone (J6/JFH1), that reproduced the acute and persistent phases of HCV infection up to 76 days of culture. We demonstrated that the acute phase of HCV infection is characterized by the elevated levels of reactive oxygen species (ROS) associated in part with an increase of NADPH-oxidase transcripts and activity and a depletion of GSH accompanied by high rates of viral replication and apoptotic cell death. Conversely, the chronic phase is characterized by a reestablishment of reduced environment due to a decreased ROS production and increased GSH content in infected cells that might concur to the establishment of viral persistence. Treatment with the prooxidant auranofin of the persistently infected cultures induced the increase of viral RNA titer, suggesting that a prooxidant state could favor the reactivation of HCV viral replication that in turn caused cell damage and death. Our results suggest that targeting the redox-sensitive host-cells pathways essential for viral replication and/or persistence may represent a promising option for contrasting HCV infection

Micro-imaging VIS-IR spectroscopy of Martian meteorites in support of the future MaMIss spectrometer measurements

In the view of the future ExoMars 2020 mission, an activity of VIS-IR spectral investigations on terrestrial and extraterrestrial Mars Analogues is ongoing, in support of the Ma Miss in situ measurements. Ma_Miss is an imaging spectrometer that works in the range 0.4-2.2 μm with 20nm spectral sampling and that will observe the lateral wall of the borehole generated by ExoMars Rover's drill (Coradini et al., 2001). In this abstract, we describe some results about the spectral properties and characterization of mineral grains of the slabs of two Martian meteorites by means of the SPIM imaging spectrometer. SPIM works in the 0.22-5.05 μm spectral range, with a spatial resolution of 38x38 μm on the sample and represents the spare of the spectrometer on Dawn spacecraft (De Angelis et al., 2015). The meteorites investigated are North West Africa 8657 (NWA8657) and Dar Al Gani 489 (DAG489), basaltic shergottites. The average spectrum of the NWA8657 slab, in comparison with spectral measurements on other martian meteorites (Mcfadden & Cline, 2005) shows low reflectance values and 1 and 2 μm spectral absorptions indicating the strong presence of Ca-pyroxenes. The successive pixel by pixel analyses for the pyroxenes spectral speciation showed a great variability of clinopyroxenes in NWA8657. In fact, the 2 μm absorption at longer wavelength in some pixel does not always correspond to the 1 μm feature at longer wavelength. The average spectrum of DAG 489 is marked by a signature typical of low-Ca pyroxenes. Pixel by pixel analyses of DAG489 shows a more homogeneous composition of the pyroxenes characterized by the two major features centered at 0.98-0.99 and 1.98-2 μm. Further spectral absorptions related to sulfates, phosphates and carbonates were detected that are being validated by SEM-BSD to constrain the formation hystories of these two shergottites

Social categorization and joint attention: Interacting effects of age, sex, and social status.

In the present study, we examine how person categorization conveyed by the combination of multiple cues modulates joint attention. In three experiments, we tested the combinatory effect of age, sex, and social status on gaze-following behaviour and pro-social attitudes. In Experiments 1 and 2, young adults were required to perform an instructed saccade towards left or right targets while viewing a to-be-ignored distracting face (female or male) gazing left or right, that could belong to a young, middle-aged, or elderly adult of high or low social status. Social status was manipulated by semantic knowledge (Experiment 1) or through visual appearance (Experiment 2). Results showed a clear combinatory effect of person perception cues on joint attention (JA). Specifically, our results showed that age and sex cues interacted with social status information depending on the modality through which it was conveyed. In Experiment 3, we further investigated our results by testing whether the identities used in Experiments 1 and 2 triggered different pro-social behaviour. The results of Experiment 3 showed that the identities resulting as more distracting in Experiments 1 and 2 were also perceived as more in need and prompt helping behaviour. Taken together, our evidence shows a combinatorial effect of age, sex, and social status in modulating the gaze following behaviour, highlighting a complex and dynamic interplay between person categorization and joint attention

CCL16/LEC powerfully triggers effector and antigen-presenting functions of macrophages and enhances T cell cytotoxicity

AbstractThe huan CC chemokine CCL16, a liver-expressed chemokine, enhances the killing activity of mouse peritoneal macrophages by triggering their expression of tumor necrosis factor α (TNF-α) and Fas ligand. Macrophages also respond to CCL16 by enhancing their production of monocyte chemoattractant protein-1, regulated on activation, normal T cells expressed and secreted chemokines, and interleukin (IL)-1β, TNF-α, and IL-12. The effect of CCL16 is almost as strong as that of lipopolysaccharide and interferon-γ, two of the best macrophage activators. Moreover, CCL16-activated macrophages overexpress membrane CD80, CD86, and CD40 costimulatory molecules and extensively phagocytose tumor cell debris. On exposure to such debris, they activate a strong, tumor-specific, cytolytic response in virgin T cells. Furthermore, cytolytic T cells generated in the presence of CCL16 display a higher cytotoxicity and activate caspase-8 in tumor target cells. This ability to activate caspase-8 depends on their overexpression of TNF-α and Fas ligand induced by CCL16. These data reveal a new function for CCL16 in the immune-response scenario. CCL16 significantly enhances the effector and the antigen-presenting function of macrophages and augments T cell lytic activity

Natural orifice endoluminal technique (NOEL) for the management of congenital duodenal membranes

Congenital Partial Duodenal Obstruction (CPDO) caused by membranes/webs/diaphragms has traditionally been managed by open or laparoscopic duodenoduodenostomy or duodenojejunostomy. We report a two center case series where Natural Orifice Endoluminal technique (NOEL) was used to treat children with CPDO

The DOF Transcription Factors in Seed and Seedling Development

The DOF (DNA binding with one finger) family of plant-specific transcription factors (TF) was first identified in maize in 1995. Since then, DOF proteins have been shown to be present in the whole plant kingdom, including the unicellular alga Chlamydomonas reinhardtii. The DOF TF family is characterised by a highly conserved DNA binding domain (DOF domain), consisting of a CX2C-X21-CX2C motif, which is able to form a zinc finger structure. Early in the study of DOF proteins, their relevance for seed biology became clear. Indeed, the PROLAMIN BINDING FACTOR (PBF), one of the first DOF proteins characterised, controls the endosperm-specific expression of the zein genes in maize. Subsequently, several DOF proteins from both monocots and dicots have been shown to be primarily involved in seed development, dormancy and germination, as well as in seedling development and other light-mediated processes. In the last two decades, the molecular network underlying these processes have been outlined, and the main molecular players and their interactions have been identified. In this review, we will focus on the DOF TFs involved in these molecular networks, and on their interaction with other proteins

Very Early Onset-IBD: evidence for the need of a multidisciplinary approach

Very early onset inflammatory bowel disease (VEO-IBD) represents approximately 25% of cases of IBD-like colitis occurring during childhood and, by definition, it is characterized by an onset prior to 6 years of age. This subgroup of patients presents significant differences from IBD occurring in older children and in adults, including a more severe clinical course, a reduced responsiveness to conventional IBD therapy, and a greater proportion of cases featuring an underlying monogenic disorder. Histological findings from gastro-intestinal (GI) biopsies are characterized by an IBD-like, apoptotic or enterocolitis-like pattern, complicating the differential diagnosis with other pediatric diseases involving GI tract. Moreover, individuals with monogenic disorders may develop significant comorbidities, such as primary immunodeficiency (PID), impacting treatment options. Without an appropriate diagnosis, the clinical course of VEO-IBD has greater potential for escalated treatment regimens involving extensive surgery, more intensive medical therapies and, even more important, inadequate recognition of underlying monogenic defect that may lead to inappropriate (sometimes fatal) therapy. For these reasons, an adequate context leading to an appropriate diagnosis is imperative, calling for a close collaboration between pediatricians, pathologists, geneticists, and immunologists

Il bacino del lago Trasimeno in epoca preistorica e protostorica. Collezioni storiche e indagini recenti

Le informazioni sulla Preistoria e sulla Protostoria della regione intorno al lago Trasimeno provengono sia da vecchie collezioni antiquarie (principalmente le Collezioni Bellucci e Calzoni, conservate al Museo Archeologico Nazionale di Perugia) che da moderne indagini sul campo (ricognizioni di superficie e scavi stratigrafici effettuati dalla Soprintendenza per i beni archeologi dell’Umbria). L'articolo fornisce una sintesi delle attuali conoscenze sul popolamento pre-protostorico di quest'area