The hepatitis B x antigen anti-apoptotic effector URG7 is localized to the endoplasmic reticulum membrane

Hepatitis B x antigen up-regulates the liver expression of URG7 that contributes to sustain chronic virus infection and to increase the risk for hepatocellular carcinoma by its anti-apoptotic activity. We have investigated the subcellular localization of URG7 expressed in HepG2 cells and determined its membrane topology by glycosylation mapping in vitro. The results demonstrate that URG7 is N-glycosylated and located to the endoplasmic reticulum membrane with an Nlumen–Ccytosol orientation. The results imply that the anti-apoptotic effect of URG7 could arise from the C-terminal cytosolic tail binding a pro-apoptotic signaling factor and retaining it to the endoplasmic reticulum membrane

Types of Corruption in Small and Micro Enterprises (SMEs) in Ibadan, Nigeria

Corruption is a phenomenon that manifests in various types and forms especially among operators of Small and Micro Enterprises (SMEs). Many actions of the operators which constitute corrupt practices often tend to be overlooked in spite of their grave consequences for the success SMEs in Nigeria. The fight against corruption in Nigeria is more concentrated in the formal sector. This study was, therefore, designed to investigate various forms in which corrupt practices are carried out among Small and Micro Enterprises in Ibadan, Nigeria. Business owners, their employees, apprentices and consumers constituted the study population. Primary data were collected using questionnaire administered on 200 business owners, 150 employees and 150 apprentices randomly chosen in five business districts in Ibadan; and the conduct of 10 in-depth interviews with purposively selected participants. Quantitative data were analysed at uni-variate level using simple percentages and frequencies while qualitative data were content analysed. Findings from the study revealed that corrupt practices were rampant among actors in SMEs and the common types of corrupt practices included stealing (60%), deception of customers (78.4%), tax evasion (62%), sale of fake products (76%), sale of expired products (65.2%), tampering with measurement scales (69.6%), bribery (82.4%), and poor service delivery (73%). The study concludes that the level of corruption in SMEs calls for concern and government should extend the fight against corruption to the informal sector in Nigeria

Predicting effective pro-apoptotic antileukaemic drug combinations using cooperative dynamic BH3 profiling

The BH3-only apoptosis agonists BAD and NOXA target BCL-2 and MCL-1 respectively and co-operate to induce apoptosis. On this basis, therapeutic drugs targeting BCL-2 and MCL-1 might have enhanced activity if used in combination. We identified anti-leukaemic drugs sensitising to BCL-2 antagonism and drugs sensitising to MCL-1 antagonism using the technique of dynamic BH3 profiling, whereby cells were primed with drugs to discover whether this would elicit mitochondrial outer membrane permeabilisation in response to BCL-2-targeting BAD-BH3 peptide or MCL-1-targeting MS1-BH3 peptide. We found that a broad range of anti-leukaemic agents–notably MCL-1 inhibitors, DNA damaging agents and FLT3 inhibitors–sensitise leukaemia cells to BAD-BH3. We further analysed the BCL-2 inhibitors ABT-199 and JQ1, the MCL-1 inhibitors pladienolide B and torin1, the FLT3 inhibitor AC220 and the DNA double-strand break inducer etoposide to correlate priming responses with co-operative induction of apoptosis. ABT-199 in combination with pladienolide B, torin1, etoposide or AC220 strongly induced apoptosis within 4 hours, but the MCL-1 inhibitors did not co-operate with etoposide or AC220. In keeping with the long half-life of BCL-2, the BET domain inhibitor JQ1 was found to downregulate BCL-2 and to prime cells to respond to MS1-BH3 at 48, but not at 4 hours: prolonged priming with JQ1 was then shown to induce rapid cytochrome C release when pladienolide B, torin1, etoposide or AC220 were added. In conclusion, dynamic BH3 profiling is a useful mechanism-based tool for understanding and predicting co-operative lethality between drugs sensitising to BCL-2 antagonism and drugs sensitising to MCL-1 antagonism. A plethora of agents sensitised cells to BAD-BH3-mediated mitochondrial outer membrane permeabilisation in the dynamic BH3 profiling assay and this was associated with effective co-operation with the BCL-2 inhibitory compounds ABT-199 or JQ1

A methodological integrated approach to analyse climate change effects in agri-food sector: The TIMES water-energy-food module

The European Union’s 2030 climate and energy policy and the 2030 Agenda for Sustainable Development underline the commitment to mitigate climate change and reduce its impacts by supporting sustainable use of resources. This commitment has become stricter in light of the ambitious climate neutrality target set by the European Green Deal for 2050. Water, Energy and Food are the key variables of the “Nexus Thinking” which face the sustainability challenge with a multi-sectoral approach. The aim of the paper is to show the methodological path toward the implementation of an integrated modeling platform based on the Nexus approach and consolidated energy system analysis methods to represent the agri-food system in a circular economy perspective (from the use of water, energy, biomass, and land to food production). The final aim is to support decision-making connected to climate change mitigation. The IEA-The Integrated MARKAL-EFOM System (TIMES) model generator was used to build up the Basilicata Water, Energy and Food model (TIMES-WEF model), which allows users a comprehensive evaluation of the impacts of climate change on the Basilicata agri-food system in terms of land use, yields and water availability and a critical comparison of these indicators in different scenarios. The paper focuses on the construction of the model’s Reference Energy and Material System of the TIMES model, which integrates water and agricultural commodities into the energy framework, and on the results obtained through the calibration of the model β version to statistical data on agricultural activities. © 2020 by the authors. Licensee MDPI, Basel, Switzerland

GC/MS sterol profiling in red blood cell membranes and plasma of newborns receiving total parenteral nutrition.

Background and Objectives: Total parenteral nutrition (TPN) is a lifesaving therapy in children with intestinal failure. frequently complicated by liver dysfunction. Plant sterols (phytosterols) of lipid emulsions have been supposed to contribute to cholestasis in TPN-treated children. The present study aimed to evaluate the plasma and red blood cell membrane (RBCM) phytosterol levels in newborns after a short period of TPN. Patients and Methods: Phytosterols, cholesterol, and other Sterol levels were quantified by gas chromatography-mass spectrometry in 15 healthy, control infants. 22 patients after TPN, and 11 patients before TPN. Sterols of lipid emulsions Were quantified. Results: Plasma and RBCM phytosterol levels were. respectively. on average 56 mu mol/L and 83 mu mol/g per protein in patient, after TPN. 13 mu mol/L and 15 mu mol/g per protein in patients before TPN. and 9 mu mol/L and 13 mu mol/g per protein in control infants (P < 0.05 for differences). The days of TPN and the total amount of infused lipids correlated significantly with RBCM phytosterol (P < 0.05): correlations for plasma were positive but not significant. No correlation was observed with plasma bilirubin, gamma-glutamyltransferase, or alanine transaminase. Conclusions: Plasma and RBCM phytosterols increase significantly in newborns after a short period of TPN. Higher phylosterol levels were observed in some patients that could have been due to their individual variability in phytosterol metabolism and/or clearance. A greater accumulation of phytosterols in membranes may induce TPN-related cholestasis. JPGN 47:645-651, 2008

Improving policy making and strategic planning competencies of public authorities in the energy management of municipal public buildings : the PrioritEE toolbox and its application in five mediterranean areas

ABSTRACT: Making public buildings smarter and more energy efficient requires tailored solutions to overcome the barriers in implementing suitable technology options in a large variety of building types. The PrioritEE project aimed to strengthen the policy-making and strategic planning competencies of local and regional public authorities in the energy management of Municipal Public Buildings, gaining experience in five local pilots in the Mediterranean area. This paper focuses on the PrioritEE toolbox, describing both the “soft components” and the technical components. These components are widely applicable and replicable in all European cities for supporting local administrations in improving energy efficiency and the use of renewable energy sources in municipal public buildings. The Energy Technologies and Building Retrofit Database is a technology repository of energy efficiency measures and renewable energy technologies, providing the main reference data on costs, technical performance and lifetime. With the Decision Support Tool users can assess current building stock energy performance, evaluate different efficiency and renewable interventions, and compare, rank, and prioritize technical options through a set of key performance indicators. A sample of the results to date in the five partner regions are also presented, comparing the main individual characteristics in order to derive replicable solutions for local authorities. This project also highlighted how crucial stakeholder involvement is for tool improvement, capacity building and enabling knowledge transfer.info:eu-repo/semantics/publishedVersio

Local Climate Mitigation and Local Climate Adaptation Plans of European Urban Audit Cities

This database shows the availability of local climate mitigation plans, local climate adaptation plans, municipal energy plans, heat wave plans and flood risk plans of all 885 Urban Audit Core Cities of the 28 countries of the European Union. Additionally, it lists per Urban Audit Core City the membership in the largest climate networks [Old Covenant of Mayors Member (2020 goal); New Covenant of Mayors Member (2030 goal); Status (1-2-3); Mayors Adapt Commitment; Compact of Mayors Member (yes/no); Compact of Mayors Stage (Badge)]. Furthermore, based on a typology of plans developed in Reckien et al., 2018 and Reckien et al., 2019, the database categorizes the plans into types, and specifies whether adaptation and mitigation aspects are jointly addressed in one plan ('joint plan')