Differential Expression of the Host Lipid Regulators ANGPTL-3 and ANGPTL-4 in HCV Infection and Treatment

Host lipid metabolism reprogramming is essential for hepatitis C virus (HCV) infection and progression to severe liver disease. Direct-acting antivirals (DAAs) achieve a sustained virological response (SVR) in most patients, but virus eradication does not always protect against hepatocellular carcinoma (HCC). Angiopoietin-like protein-3 (ANGPTL-3) and angiopoietin-like protein-4 (ANGPTL-4) regulate the clearance of plasma lipids by inhibiting cellular lipase activity and possess emerging roles in tumourigenesis. We used ELISA and RT-qPCR to investigate ANGPTL-3 and ANGPTL-4 expression in HCV patients with characterised fibrosis throughout the natural history of hepatitis C and in long-term HCV infection in vitro, before and after DAA treatment. ANGPTL-3 was decreased in patients with advanced fibrosis compared to other disease stages, while ANGPTL-4 was progressively increased from acute infection to cirrhosis and HCC, peaking at the advanced fibrosis stage. Only ANGPTL-3 mRNA was down-regulated during early infection in vitro, although both ANGPTLs were increased later. DAA treatment did not alter ANGPTL-3 levels in advanced fibrosis/cirrhosis and in HCV infection in vitro, in contrast to ANGPTL-4. The association between ANGPTLs and fibrosis in HCV infection was underlined by an inverse correlation between the levels of ANGPTLs and serum transforming growth factor- β (TGF-β). Collectively, we demonstrate the pivotal role of advanced fibrosis in defining the expression fate of ANGPTLs in HCV infection and after treatment and propose a role for ANGPTL-3 as a contributor to post-treatment deregulation of lipid metabolism that could predispose certain individuals to HCC development.     

Heterogeneities in Cell Cycle Checkpoint Activation Following Doxorubicin Treatment Reveal Targetable Vulnerabilities in TP53 Mutated Ultra High-Risk Neuroblastoma Cell Lines

Most chemotherapeutics target DNA integrity and thereby trigger tumour cell death through activation of DNA damage responses that are tightly coupled to the cell cycle. Disturbances in cell cycle regulation can therefore lead to treatment resistance. Here, a comprehensive analysis of cell cycle checkpoint activation following doxorubicin (doxo) treatment was performed using flow cytometry, immunofluorescence and live-cell imaging in a panel of TP53 mutated ultra high-risk neuroblastoma (NB) cell lines, SK-N-DZ, Kelly, SK-N-AS, SK-N-FI, and BE(2)-C. Following treatment, a dose-dependent accumulation in either S- and/or G2/M-phase was observed. This coincided with a heterogeneous increase of cell cycle checkpoint proteins, i.e., phos-ATM, phos-CHK1, phos-CHK2, Wee1, p21^Cip1/Waf1, and p27^Kip among the cell lines. Combination treatment with doxo and a small-molecule inhibitor of ATM showed a delay in regrowth in SK-N-DZ, of CHK1 in BE(2)-C, of Wee1 in SK-N-FI and BE(2)-C, and of p21 in Kelly and BE(2)-C. Further investigation revealed, in all tested cell lines, a subset of cells arrested in mitosis, indicating independence on the intra-S- and/or G2/M-checkpoints. Taken together, we mapped distinct cell cycle checkpoints in ultra high-risk NB cell lines and identified checkpoint dependent and independent druggable targets.     

Comparative study of visible light polymerized gelatin hydrogels for 3D culture of hepatic progenitor cells

Photopolymerization techniques have been widely used to create hydrogels for biomedical applications. Visible light‐based photopolymerizations are commonly initiated by type II (i.e., noncleavage‐type) photoinitiator in conjunction with a coinitiator. On the other hand, type I photoinitiators (i.e., cleavage type) are rarely compatible with visible light‐based initiation due to their limited molar absorbability in the visible light wavelengths. Here, we report visible light initiated orthogonal photoclick crosslinking to fabricate gelatin‐norbornene and poly(ethylene glycol)‐tetra‐thiol hydrogels using either cleavage‐type (i.e., lithium acylphosphinate, LAP) or noncleavage‐type photoinitiator (i.e., eosin‐Y, EY) without the use of a coinitiator. Regardless of the initiator type, the step‐growth gelatin‐PEG hybrid hydrogels crosslinked and degraded similarly. While both systems exhibited similar cytocompatibility for hepatic progenitor HepaRG cells, gelation initiated by noncleavage‐type initiator EY afforded slightly higher degree of hepatic gene expression. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 44585.     

A Unified Network Selection Framework Using Principal Component Analysis and Multi Attribute Decision Making

Services are ubiquitously delivered over multiple wireless access technologies in a heterogeneous wireless network environment. A significant issue is the ranking of the alternative access networks and the selection of the most efficient and suitable one in order to meet the Quality of Service (QoS) requirements of a specific service, as these are defined by the user. With this way, the user receives enhanced Quality of Experience. However, decisions on which network to connect are usually difficult to be reached, since multiple factors of different importance have to be taken into consideration. The subject of the paper is the introduction of a novel unified network selection framework. A framework for defining decision criteria weights relying on the variance of network measurements is also provided. For this purpose, Principal Component Analysis and Analytic Hierarchy Process are deployed so as to unravel the patterns in data and retrieve parameter weights through pair wise comparisons respectively. The framework addresses the final network selection by the employment of Multi Attribute Decision Making methods and by using certain QoS indicators acting as figures of merit which influence the decision process. Finally, the proposed scheme is tested through extended simulations and a discussion over its performance is made. Some useful conclusions are drawn.     

XI. Yeast sequencing reports. The complete sequencing of a 24·6 kb segment of yeast chromosome XI identified the known loci URA1, SAC1 and TRP3, and revealed 6 new open reading frames including homologues to the threonine dehydratases,membrane transporters,hydantoinases and the phospholipase A2-activating protein

We report the entire sequence of a 26·4 kb segment of chromosome XI of Saccharomyces cerevisiae. Identification of the known loci URA1, TRP3 and SAC1 revealed a translocation compared to the genetic map. Additionally, six unknown open reading frames have been identified. One of them is similar to catabolic threonine dehydratases. Another one contains characteristic features of membrane transporters. A third one is homologous in half of its length to the prokaryotic hydantoinase HyuA and in the other half to hydatoinase HyuB. A fourth one is homologous to the mammalian phospholipase A₂-activating protein. A fifth one, finally, is homologous to the hypothetical open reading frame YCR007C of chromosome III. The sequence has been deposited in the EMBL data library under Accession Number X75951.     

Digital technology and innovation trajectories in the Mediterranean region: A casualty of or an antidote to the economic crisis?

Weak macroeconomic conditions mean admittedly that government spending on Information and Communication Technologies (ICTs) is reduced and consequently that ICT-related policies are scrutinized for their necessity, efficiency and impact on growth. At the same time, such conditions bring into the spotlight and set priority to measures targeting the ICT sector and promoting ICT-based innovation as a means of pursuing economic recovery. The 2008 financial crisis affected severely several parts of the world and particularly the Mediterranean region, where, even today, several years after the start of this economic turmoil in Europe, finding an effective response to mitigating the consequences of recession is still pertinent. Building on previous literature that recognizes ICT-based innovation as a crisis mitigation enabler, this paper propels discussion on the association among ICT- and innovation-oriented indicators and the economic crisis context in four Mediterranean countries, namely Spain, Greece, Italy and Cyprus. In this respect, it leverages a set of open and credible indicators of both technological and economic character and attempts to reflect on the effects of the crisis on ICT or conversely seen the potential of the latter to enable the affected countries to come out of the crisis.     

In-stream biogeochemical processes of a temporary river

A reach at the estuary of Krathis River in Greece was used to assess how in-stream processes alter its hydrologic and biogeochemical regime. Krathis River exhibited high annual flow variability and its transmission losses become significant, especially during the dry months. These transmission losses are enhanced in chemistry due to release of nutrients from river sediments. These fluxes are significant because they correspond to 11% of the dissolved inorganic nitrogen flux of the river. Release of nitrogen species was influenced by temperature, while release of phosphate was not because phosphate levels were below the equilibrium concentration. There is a significant amount of sediments with fine composition that create "hot spot" areas in the river reach. These sediments are mobilized during the first flush events in the fall carrying with them a significant load of nutrient and suspended matter to the coastal zone. The nutrient organic content of sediments was also significant and it was studied in terms of its mineralization capacity. The capacity for mineralization was influenced by soil moisture, exhibiting significant capacity even at moisture levels of 40%. Temporary rivers are sensitive ecosystems, vulnerable to climate changes. In-stream processes play a significant role in altering the hydrology and biogeochemistry of the water and its impacts to the coastal zone.