ATTRACTIVE DANUBE Project – Territorial Attractiveness Analysis of the Danube Region

Following integrative approach of the European Spatial Development Perspective (ESDP) for achieving balanced and sustainable territorial development in Europe, European Union (EU) has launched the European Observation Network for Territorial Development and Cohesion (ESPON) programme to research and identify integrative territorial evidence models for the different EU development policies monitoring and evaluation. Among the others, territorial evidence model for a territorial attractiveness (TA) monitoring was developed as result of the ESPON’s ATTREG project, since TA has been recognized by the different EU policies as one of those complex territorial qualities important for the European competitiveness and territorial cohesion. Defined as a set of territorial capitals and assets with capacities to retain existing and attract new resources, policy-supported TA is able to create or improve territorial identity –i.e. competitive advantage- needed for reaching inclusive, smart and sustainable development goals on different levels within EU and its cross-border regions. Thus, targeting the EU Strategy for the Danube Region (EUSDR) goals, and relying on the INTERREG Danube Transnational Programme (DTP) instrument, the Improving Capacities for Enhancing Territorial Attractiveness of the Danube Region (Attractive Danube) project has been launched in 2017 with the aim to build a TA monitoring system in the Danube Region. This system should support both national TA policy priorities identification and monitoring, as well as transnational TA policies coordination among the 11 partner-countries (including Austria) in the Danube macroregion. The purpose of this paper is to present the initial findings of TA analysis for the Danube Region, using the results achieved during the first year of the Attractive Danube project implementation. The project objectives and activities in 2017 included: 1) data collection for the selected TA indicators, and 2) building national and transnational TA monitoring platforms, namely 11 national TAMPs and transnational CO TAMP. The focus of this paper is on the 22 common TA indicators analysis based on their values collected by the project partners for period 2008-2016. In order for the TA disparities and trends to be identified and, thus, needed TA policy improvements to be defined, methodology applied for this TA indicator analysis was compiled using the approaches elaborated and modelled by the other ESPON projects, namely INTERCO and KITCASP projects. As an initial result, it is found that positive TA cohesion trend was prevailing one and that there was no common TA indicator with strong territorial disparity trend in period 2008-2016. Therefore, in this paper, after the Attractive Danube project’s aim and objectives description, the TA as development concept is presented. Then, methodological approaches to the TA indicators data collection and analysis are defined. Finally, the main results and initial findings of the TA indicators analysis for the Danube Region are presented and interpreted, and general conclusions on possible TA policy improvements towards territorial cohesion and sustainability in future in this macroregion are made

“Attractive Danube” – Improving Capacities for Enhancing Territorial Attractiveness of the Danube Region

Since the launching of the European Observation Network for Territorial Development and Cohesion (ESPON) programme in 2002, as the initiative for territorial monitoring of the EU Cohesion Policy implementation and results evaluation against the European Spatial Development Perspective (ESDP) goals, the number, variation and specialization of the territorial monitoring systems for development policies implementation in Europe have been growing stadily. And, although these territorial monitoring systems are differening among themselves in respect to the specific goals they are aspiring and/or territorial units they are using for analyses, common for all of them is support to the vision of cohesive, smart and sustainable territorial development throughout EU and its cross-border regions up till 2020. The purpose of this paper is to present the Attractive Danube project, which aim is to build a territorial monitoring system to support the transnational territorial attractiveness policy priorities identification, implementation and evaluation within the Danube Region. Implementing in period 2017-2019 under the Interreg’s Danube Transnational Cooperation (DTP) programme, this project has a goal to improve the transnational governance and institutional capacities of 11 countries (Slovenia, Hungary, Czech Republic, Slovakia, Germany, Bulgaria, Romania, Serbia, Croatia, Montenegro and Bosnia and Herzegovina) to enhance their competitive advantages by the better understanding and management of the national social, economic and environmental development potentials within the Danube macroregion. Thus, in this paper, after the Attractive Danube project’s background, aim, goals and methodology description, the territorial attractiveness concept, indicators and monitoring tool would be presented. Afterwards, the approach to improvement of stakeholders’ capacities for the territorial attractiveness understanding and management as well as national and transnational policies integration is described. Finally, along with the information on current project status and planned activities in future, conclusions on the expected project’s outcomes is made

Oligomerization of HEXIM1 via 7SK snRNA and coiled-coil region directs the inhibition of P-TEFb

Transcriptional elongation of most eukaryotic genes by RNA polymerase II requires the kinase activity of the positive transcription elongation factor b (P-TEFb). The catalytically active P-TEFb complex becomes inactive when sequestered into the large complex by the cooperative actions of 7SK snRNA and HEXIM1. In this study, we report that HEXIM1 forms oligomers in cells. This oligomerization is mediated by its predicted coiled-coil region in the C-terminal domain and 7SK snRNA that binds a basic region within the central part of HEXIM1. Alanine-mutagenesis of evolutionary conserved leucines in the coiled-coil region and the digestion of 7SK snRNA by RNase A treatment prevent this oligomerization. Importantly, mutations of the N-terminal part of the coiled-coil region abrogate the ability of HEXIM1 to bind and inhibit P-TEFb. Finally, the formation of HEXIM1 oligomers via the C-terminal part of the coiled-coil or basic regions is critical for the inhibition of transcription. Our results suggest that two independent regions in HEXIM1 form oligomers to incorporate P-TEFb into the large complex and determine the inhibition of transcriptional elongation

HMBA Releases P-TEFb from HEXIM1 and 7SK snRNA via PI3K/Akt and Activates HIV Transcription

Hexamethylene bisacetamide (HMBA) is a potent inducer of cell differentiation and HIV production in chronically infected cells. However, its mechanism of action remains poorly defined. In this study, we demonstrate that HMBA activates transiently the PI3K/Akt pathway, which leads to the phosphorylation of HEXIM1 and the subsequent release of active positive transcription elongation factor b (P-TEFb) from its transcriptionally inactive complex with HEXIM1 and 7SK small nuclear RNA (snRNA). As a result, P-TEFb is recruited to the HIV promoter to stimulate transcription elongation and viral production. Despite the continuous presence of HMBA, the released P-TEFb reassembles rapidly with 7SK snRNA and HEXIM1. In contrast, a mutant HEXIM1 protein that cannot be phosphorylated and released from P-TEFb and 7SK snRNA via the PI3K/Akt pathway antagonizes this HMBA-mediated induction of viral production. Thus, our studies reveal how HIV transcription is induced by HMBA and suggest how modifications in the equilibrium between active and inactive P-TEFb could contribute to cell differentiation

A New Paradigm in Eukaryotic Biology: HIV Tat and the Control of Transcriptional Elongation

Studies of the transcriptional transactivator (Tat), a key regulatory protein of HIV, have yielded insight into the control of eukaryotic transcriptio

ISTER: Connecting Historical Danube Regions Roman Routes with a GIS-based Territorial Atlas and an Online Interactive Tool

REAL CORP 2022 Proceedings/Tagungsband 14-16 November 2022 – https://www.corp.at ISBN 978-3-9504945-1-8. Editors: M. SCHRENK, V. V: POPOVICH, P. ZEILE, P. ELISEI, C.BEYER, J. RYSER 1045 ISTER: Connecting Historical Danube Regions Roman Routes with a GIS-based Territorial Atlas and an Online Interactive Tool Blaž Barborič, Clemens Beyer, Georg Neugebauer, Manfred Schrenk (Blaž Barborič, MSc, Geodetic Institute of Slovenia, Jamova cesta 2, 1000, Ljubljana, Slovenia; [email protected]) (Dipl.-Ing. Manfred Schrenk, Department of Spatial, Landscape and Infrastructure Sciences, Institute of Spatial Planning, Environmental Planning and Land Rearrangement (IRUB), Peter-Jordan-Straße 82, 1190 Vienna, Austria, [email protected]) (Dipl.-Ing. Clemens Beyer, Department of Spatial, Landscape and Infrastructure Sciences, Institute of Spatial Planning, Environmental Planning and Land Rearrangement (IRUB), Peter-Jordan-Straße 82, 1190 Vienna, Austria, [email protected]) (Dr. Georg Neugebauer, Department of Spatial, Landscape and Infrastructure Sciences, Institute of Spatial Planning, Environmental Planning and Land Rearrangement (IRUB), Peter-Jordan-Straße 82, 1190 Vienna, Austria, [email protected]) 1 ABSTRACT ISTER project addresses the challenge of Roman heritage discontinuity. Stepping further the isolated Roman settlements heritage, ISTER tackles the territorial dimension of the Roman Routes, as a contiguous transnational element that passes national borders acreoss the Danube region and provides a relevant scale for exchange and joint development. Therefore, ISTER’s main objective focuses on rediscovering and revitalizing the ancient Roman Roads Network along the Danube river as a key driver in promoting territorial development based on sustainable use of cultural and natural heritage. During the project, data from all local and regional partners were collected, sorted and harmonised. Based on a user requirements survey, a strategy for the deployment of the ISTER Interactive Tool was developed. The interactive tool uses the collected data and geodata for an open orientation and information platform which aims to foster knowledge about the Roman cultural heritage in the broad public. The ISTER Interactive Tool is set up as a responsive website to be used with mobile devices like smartphones or tablets. The central element of the interactive tool is a map, all information is queried from a central database as location-based service. The tool does not only provide information about the cultural heritage elements (monuments, milestones), but also provides other information which can be useful when planning a trip, like places to eat or drink, accommodation facilities, public transport stops, or supermarkets. It is available not only in English, but also in the local languages of the ISTER project partners

Cracking the control of RNA polymerase II elongation by 7SK snRNP and P-TEFb

Release of RNA polymerase II (Pol II) from promoter-proximal pausing has emerged as a critical step regulating gene expression in multicellular organisms. The transition of Pol II into productive elongation requires the kinase activity of positive transcription elongation factor b (P-TEFb), which is itself under a stringent control by the inhibitory 7SK small nuclear ribonucleoprotein (7SK snRNP) complex. Here, we provide an overview on stimulating Pol II pause release by P-TEFb and on sequestering P-TEFb into 7SK snRNP. Furthermore, we highlight mechanisms that govern anchoring of 7SK snRNP to chromatin as well as means that release P-TEFb from the inhibitory complex, and propose a unifying model of P-TEFb activation on chromatin. Collectively, these studies shine a spotlight on the central role of RNA binding proteins (RBPs) in directing the inhibition and activation of P-TEFb, providing a compelling paradigm for controlling Pol II transcription with a non-coding RNA.Peer reviewe

Tat competes with HEXIM1 to increase the active pool of P-TEFb for HIV-1 transcription

Human immunodeficiency virus type 1 (HIV-1) transcriptional transactivator (Tat) recruits the positive transcription elongation factor b (P-TEFb) to the viral promoter. Consisting of cyclin dependent kinase 9 (Cdk9) and cyclin T1, P-TEFb phosphorylates RNA polymerase II and the negative transcription elongation factor to stimulate the elongation of HIV-1 genes. A major fraction of nuclear P-TEFb is sequestered into a transcriptionally inactive 7SK small nuclear ribonucleoprotein (snRNP) by the coordinated actions of the 7SK small nuclear RNA (snRNA) and hexamethylene bisacetamide (HMBA) induced protein 1 (HEXIM1). In this study, we demonstrate that Tat prevents the formation of and also releases P-TEFb from the 7SK snRNP in vitro and in vivo. This ability of Tat depends on the integrity of its N-terminal activation domain and stems from the high affinity interaction between Tat and cyclin T1, which allows Tat to directly displace HEXIM1 from cyclin T1. Furthermore, we find that in contrast to the Tat-independent activation of the HIV-1 promoter, Tat-dependent HIV-1 transcription is largely insensitive to the inhibition by HEXIM1. Finally, primary blood lymphocytes display a reduced amount of the endogenous 7SK snRNP upon HIV-1 infection. All these data are consistent with the model that Tat not only recruits but also increases the active pool of P-TEFb for efficient HIV-1 transcription

PKC phosphorylates HEXIM1 and regulates P-TEFb activity

WOS:000309927100040Peer reviewe

HEXIM1 targets a repeated GAUC motif in the riboregulator of transcription 7SK and promotes base pair rearrangements

7SK snRNA, an abundant RNA discovered in human nucleus, regulates transcription by RNA polymerase II (RNAPII). It sequesters and inhibits the transcription elongation factor P-TEFb which, by phosphorylation of RNAPII, switches transcription from initiation to processive elongation and relieves pauses of transcription. This regulation process depends on the association between 7SK and a HEXIM protein, neither isolated partner being able to inhibit P-TEFb alone. In this work, we used a combined NMR and biochemical approach to determine 7SK and HEXIM1 elements that define their binding properties. Our results demonstrate that a repeated GAUC motif located in the upper part of a hairpin on the 5′-end of 7SK is essential for specific HEXIM1 recognition. Binding of a peptide comprising the HEXIM Arginine Rich Motif (ARM) induces an opening of the GAUC motif and stabilization of an internal loop. A conserved proline-serine sequence in the middle of the ARM is shown to be essential for the binding specificity and the conformational change of the RNA. This work provides evidences for a recognition mechanism involving a first event of induced fit, suggesting that 7SK plasticity is involved in the transcription regulation