Tandem mass spectrometry for the structural determination of backbone-modified peptides

AbstractA variety of backbone-modified peptides were desorbed by fast atom bombardment and collisionally activated. These peptide modifications involve the replacement of a normal [CONH] peptide linkage with such groups as thiomethylene ether (CH2S), thioamide (CSNH), methyleneamine (CH2NH), and thiomethylene sulfoxide (CH2SO) moieties. Modified linear peptides decompose to give fragmentations characteristic of the modifications as well as typical peptide bond fragments. The presence of a replacement group in cyclic peptides can induce new fragmentations. The presence of other functional groups, such as exocyclic N-terminal residue, however, can dominate the observed fragmentations. Upon collisional activation, unmodified linear peptides fragment to give N-terminal ions as the most abundant daughter ions. In comparison, ψ[CH2NH] and ψ[CH2S] modified linear peptides decompose to give prominent C-terminal sequence ions. The ψ[CH2SO] modified linear peptides, however, fragment in both N- and C-terminal ions of high relative abudance. Depending on the modification, daughter ions or internal fragment ions are observed that are characteristic of the amide bond replacement. Useful structural information can therefore be obtained

The burden of hepatocellular carcinoma in non-alcoholic fatty liver disease: Screening issue and future perspectives

In recent decades, non-alcoholic fatty liver disease (NAFLD) has become the most common liver disease in the Western world, and the occurrence of its complications, such as hepatocellular carcinoma (HCC), has rapidly increased. Obesity and diabetes are considered not only the main triggers for the development of the disease, but also two independent risk factors for HCC. Single nucleotide polymorphisms (such as PNPLA3, TM6SF2 and MBOAT7) are related to the susceptibility to the development of HCC and its progression. Therefore, an appropriate follow-up of these patients is needed for the early diagnosis and treatment of HCC. To date, international guidelines recommend the use of ultrasonography with or without alpha-fetoprotein (AFP) in patients with advanced fibrosis. Furthermore, the use of non-invasive tools could represent a strategy to implement surveillance performance. In this review, we analyzed the main risk factors of NAFLD-related HCC, the validated screening methods and the future perspectives

Why Real Citizens Would Turn to Artificial Leaders

Governments are increasingly using artificial intelligence to improve workflows and services. Applications range from predicting climate change, crime, and earthquakes to flu outbreaks, low air quality, and tax fraud. Artificial agents are already having an impact on eldercare, education, and open government, enabling users to complete procedures through a conversational interface. Whether replacing humans or assisting them, they are the technological fix of our times. In two experiments and a follow-up study, we investigate factors that influence the acceptance of artificial agents in positions of power, using attachment theory and disappointment theory as explanatory models. We found that when the state of the world provokes anxiety, citizens perceive artificial agents as a reliable proxy to replace human leaders. Moreover, people accept artificial agents as decision-makers in politics and security more willingly when they deem their leaders or government to be untrustworthy, disappointing, or immoral. Finally, we discuss these results with respect to theories of technology acceptance and the delegation of duties and prerogatives

Pharmacological therapy of non-alcoholic fatty liver disease: What drugs are available now and future perspectives

The non-alcoholic fatty liver disease (NAFLD) is rapidly becoming the most common cause of chronic liver disease as well as the first cause of liver transplantation. NAFLD is commonly associated with metabolic syndrome (MetS), and this is the most important reason why it is extremely difficult to treat this disease bearing in mind the enormous amount of interrelationships between the liver and other systems in maintaining the metabolic health. The treatment of NAFLD is a key point to prevent NASH progression to advanced fibrosis, to prevent cirrhosis and to prevent the development of its hepatic complications (such as liver decompensation and HCC) and even extrahepatic one. A part of the well-known healthy effect of diet and physical exercise in this setting it is important to design the correct pharmaceutical strategy in order to antagonize the progression of the disease. In this regard, the current review has the scope to give a panoramic view on the possible pharmacological treatment strategy in NAFLD patients

Seismo-stratigraphic and morpho-bathymetric analysis revealing recent fluid-rising phenomena on the Adventure Plateau (northwestern Sicily Channel)

The northwestern region of the Sicily Channel hosts a great number of morphological highs, the widest of which is the Adventure Plateau that is part of the Sicilian Maghrebian Fold and Thrust Belt system, formed since the Neogene. The Adventure Plateau was shaped in the Early Pliocene by an extensional phase that produced high-angle normal faults mostly WNW-ESE to N-S oriented. Through these faults, magmatic fluids ascended and produced widespread volcanic manifestations often associated to fluid flow processes. The interpretation of multibeam echosounder, seismic reflection (sparker, airgun) and well-log data allow us to identify several features related to the presence of fluids in the study area. The morpho-structural analysis showed a NW–SE oriented fault system and a string of pockmarks that follow the same trend. A detailed well-log analysis confirmed the presence of oil traces, at a depth of ~ 250 m, and gas (i.e., CO2) at a depth of ~ 450 m. The seismo-stratigraphic analysis highlighted seismic signals located below the pockmarks, (e.g. seismic chimneys, bright spots) which suggest the presence of fluids that would rise to a few meters’ depth. Based on the observations, two sources and two corresponding rising mechanisms have been identified. Morphometric analysis of pockmarks has been performed to delineate their possible interaction with the bottom currents. A fluids pathway model has been reconstructed, revealing the source of fluids emissions at depth in the Adventure Plateau, and providing new insights into the identification of fluid leakage pathways

Immunohistochemical expression of apoptotic factors, cytokeratins, and metalloproteinase-9 in periapical and epithelialized gingival lesions

The aim of the study was to assess the involvement of apoptotic factors, cytokeratins and metalloproteinase- 9 in the histogenesis of both Epithelialized Gingival Lesions (EGL) and Periapical Lesions (PAL). 55 consecutive patients, 30 with PAL and 25 with EGL, were selected for the study after clinical and radiological examinations. The PAL patients had severe periapical lesions and tooth decay with exposure of the pulp chamber. All PAL and EGL biopsies were surgically extracted, fixed in 10% buffered formalin, and processed for routine light microscopy. Ten biopsies of each category were processed for immunohistochemistry (IHC). Serial paraffin sections were stained by IHC with appropriate antibodies to detect cytokeratins (CKs) 1, 5, 8, 10 and 14, caspase-3 and -9, metalloproteinase-9, and for PCNA and TUNEL assays. Both PAL and EGL showed a high expression of the cytokeratin 1, 5 and 8 with higher expression in EGL. Moreover, CK10 was markedly less intense expressed in EGL compared to PAL, while CK14 was almost three times stronger expressed in EGL. The expression of caspase-3 and -9 was stronger in PAL compared to EGL, however, the difference was only significant for caspase-9. In PAL apoptosis detected by TUNNEL method and the expression of MMP-9 were higher than in EGL, whereas PCNA was significantly more expressed in EGL. The results clearly suggest that both lesions have exclusively an epithelial origin and that epithelial proliferation was correlated with the degree of apoptosis in both entities. PAL and EGL presented mostly similar cytokeratin expression except for CK10 and CK14, though with marked differences in the distribution and intensity of IHC reactions. Finally, the degradation of extracellular matrix in both lesions could be partially attributed to the strong presence of MMP-9. (Folia Histochemica et Cytobiologica 2012, Vol. 50, No. 4, 497\u2013503

Morphology of the submerged Ferdinandea Island, the ‘Neverland’ of the Sicily Channel (central Mediterranean Sea)

We present the bathy-morphological map at a scale of 1: 50,000 of the area around the submerged Ferdinandea Island, the ‘Neverland’ of the Sicily Channel (central Mediterranean Sea). We investigate an area of 100 km2, between 10 and 350 m, which is part of a triangular morphological high, 360 km2 wide, representing the SE-wards prolongation of the Adventure Bank. The study is based on the morphometric analysis based on high resolution multibeam, and sub-bottom CHIRP profiles collected in 2015. The area around the remains of Ferdinandea Island is morphologically shaped by the interplay between volcanic, tectonic, fluid seepage, and oceanographic processes. Since the study area is considered a hot spot of biodiversity affected by maritime traffic (especially in Ferdinandea Channel) and hosting communication pipelines, this map provides insights both for habitat mapping purposes and preliminary marine geohazard assessment due to the occurrence of historically active submarine volcanoes, pockmarks, and mass transport deposits

A Prospective Observational Study on the Role of Immunohistochemical Expression of Orphanin in Laryngeal Squamous Cell Carcinoma Recurrence

To date, histological biomarkers expressed by laryngeal cancer are poorly known. The identification of biomarkers associated with laryngeal squamous cell carcinoma (SCC), would help explain the tumorogenesis and prevent the possible recurrence of the lesion after treatment. For this reason, the aim of this study is to investigate, for the first time, the Orphanin expression in 48 human specimens of laryngeal SCC and evaluate its possible correlation with patients prognosis. We analyzed pathological specimens from 48 patients with laryngeal SCC to detect the presence of Orphanin by using an immunohistochemistry test. We compared the findings with healthy tissue acquired from patients who underwent surgery for mesenchymal benign tumours of the larynx. The specimens were stained with anti-Orphanin monoclonal antibodies. Results were processed through a computerised image analysis system to determine a scale of staining intensity. All the tumoural specimens examined showed a significant immunoreaction for Orphanin when compared with healthy tissues (p < 0.05) but with a different immune reactivity related to clinical-pathological features. A high Orphanin expression was not significantly related to Histological Grading (HG), TNM, and stage (p > 0.05). In the multivariate analysis, the Orphanin expression was significantly related only to the malignant recurrence (p < 0.05). Our study suggests that Orphanin could have a role in tumorigenesis by increasing the recurrence of cancer; therefore, it should be further explored as a possible biomarker for laryngeal cancer

Temporal Control of the Host-Guest Properties of a Calix[6]arene Receptor by the Use of a Chemical Fuel

The host-guest interaction of a 1,3,5-trisaminocalix[6]arene receptor with N-methylisoquinolinium trifluoromethanesulfonate (Kassof 500 ± 30 M-1in CD2Cl2) can be dissipatively driven by means of 2-cyano-2-(4′-chloro)phenylpropanoic acid used as a convenient chemical fuel. When the fuel is added to a dichloromethane solution containing the above complex, the host is induced to immediately release the guest in the bulk solution. Consumption of the fuel allows the guest to be re-uptaken by the host. The operation can be satisfactorily reiterated with four subsequent additions of fuel, producing four successive release-reuptake cycles. The percentage of the guest temporarily released in the bulk solution by the host and the time required for the reuptake process can be finely regulated by varying the quantities of added fuel

Comparison of video-assisted pleurectomy/decortication surgery plus hyperthermic intrathoracic chemotherapy with VATS talc pleurodesis for the treatment of malignant pleural mesothelioma: A pilot study

Hyperthermic intrathoracic chemotherapy (HITHOC) adjunct to surgery for Malignant Pleural Mesothelioma (MPM) has no definite role. The primary objective of this pilot-trial was to evaluate the feasibility for future large studies. The study design was a prospective randomized three-centric pilot trial. We recruited patients diagnosed with MPM and prospectively assigned them to two groups: Group A: Video Assisted Thoracic Surgery (VATS) talc pleurodesis or Group B: Video-assisted P/D plus HITHOC. From November-2011 to July-2017 24 males and 3 females, with a median age of 68-years were enrolled (recruitment rate 5 patients/year). Preoperative stage was I-II, and 18 had epithelioid type. 14 patients were in the Group A. Operative mortality was 0. Follow-up ranged 6–80 months. The median overall survival time started to diverge at 20 months, being 19 months (95% CI 12–25) in Group A and 28 months (95% CI 0–56) in Group B. Survival rate for the epithelioid type was 15 months (95% CI 0–34) in Group A and 45 months (95% CI 0–107) in the Group B. These findings suggest that video-assisted P/D plus HITHOC may improve survival time in MPM patients undergoing surgical treatment and support the need for a larger multicenter randomized clinical trial