Outsourcing dei sistemi informativi in Italia

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ISEK⁴ – A Regional Approach to Inner City Development

Integrated planning approaches provide the toolkit for delivering holistic and interdisciplinary solutions to meet the complex challenges of the 21st century. However, established instruments such as the integrated urban development concept (ISEK, common in Germany) lack the multilevel spatial integration required to tackle these issues effectively. Designed as a pilot project for the development of a new planning instrument, ISEK⁴ addressed two spatial spheres that – despite obvious necessity – are rarely considered together in the existing planning toolkit: the inner city and the functional region. Within eight months, integrated urban development concepts for the inner cities of Bruneck (South Tyrol), Hermagor-Pressegger See (Upper Carinthia), Lienz (East Tyrol), and Spittal an der Drau (Upper Carinthia) were developed along with a regional symbiosis of the SOUTH ALPINE SPACE, demonstrating and using synergies between the inner cities as anchor points of public life in the region. The ISEK⁴ project was based on a transdisciplinary planning approach and developed together with local steering groups from the cities. During the project, knowledge and needs were collected, recorded, and spatially contextualized in different workshop settings. In the work process, a mixed methods approach comprised of qualitative (GIS accessibility analyses, heat mapping) and qualitative (visioneering, storytelling, document analysis, design thinking lab, etc.) planning and research methods was employed. The central outcome of the ISEK⁴ project was a joint regional vision of the future, in both which local potentials and characteristics as well as regional strategies for action are represented. Alongside a geographically warped future image of the region, a vision story was used to outline the key areas of joint action. The ISEK⁴ concept also contains four city-specific sections (local ISEKs) drawing upon the so-called regional guiding principles, which are combined in one joint document. The key innovation of the project was the simultaneous consideration of four municipal city centres within a regional framework. It was shown that through the symbiosis of multiple concepts, activities in the field of inner-city development can be bundeled strategically and, in many cases, also implemented together. This paper focuses on the work process, the lessons learned and the transferability of the project approach, as well as selected results. A special focus will be on the methodological aspects of the storytelling method that was employed in the design of the regional and local future visions for ISEK⁴

COMMD7 as a novel NEMO interacting protein involved in the termination of NF-κB signaling

NEMO/IKKγ is the regulatory subunit of the IκB Kinase (IKK) complex, required for the activation of the NF-κB pathway, which is involved in a variety of key processes, including immunity, inflammation, differentiation, and cell survival. Termination of NF-κB activity on specific -κB responsive genes, which is crucial for the resolution of inflammatory responses, can be achieved by direct degradation of the chromatin-bound NF-κB subunit RelA/p65, a process mediated by a protein complex that contains Copper Metabolism Murr1 Domain 1 (COMMD1). In this study, we identify COMMD7, another member of the COMMDs protein family, as a novel NEMO-interacting protein. We show that COMMD7 exerts an inhibitory effect on NF-κB activation upon TNFα stimulation. COMMD7 interacts with COMMD1 and together they cooperate to down-regulate NF-κB activity. Accordingly, termination of TNFα-induced NF-κB activity on the -κB responsive gene, Icam1, is defective in cells silenced for COMMD7 expression. Furthermore, this impairment is not greatly increased when we silence the expression of both COMMD7 and COMMD1 indicating that the two proteins participate in the same pathway of termination of TNFα-induced NF-κB activity. Importantly, we have demonstrated that COMMD7's binding to NEMO does not interfere with the binding to the IKKs, and that the disruption of the IKK complex through the use of the NBP competitor impairs the termination of NF-κB activity. We propose that an intact IKK complex is required for the termination of NF-κB-dependent transcription and that COMMD7 acts as a scaffold in the IKK-mediated NF-κB termination

EDA-ID and IP, Two Faces of the Same Coin: How the Same IKBKG / NEMO Mutation Affecting the NF-B Pathway Can Cause Immunodeficiency and/or Inflammation

Anhidrotic Ectodermal Dysplasia with ImmunoDeficiency (EDA-ID, OMIM 300291) and Incontinentia Pigmenti (IP, OMIM 308300) are two rare diseases, caused by mutations of the IKBKG/NEMO gene. The protein NEMO/IKKγ is essential for the NF-κB activation pathway, involved in a variety of physiological and cellular processes, such as immunity, inflammation, cell proliferation, and survival. A wide spectrum of IKBKG/NEMO mutations have been identified so far, and, on the basis of their effect on NF-κB activation, they are considered hypomorphic or amorphic (loss of function) mutations. IKBKG/NEMO hypomorphic mutations, reducing but not abolishing NF-κB activation, have been identified in EDA-ID and IP patients. Instead, the amorphic mutations, abolishing NF-κB activation by complete IKBKG/NEMO gene silencing, cause only IP. Here, we present an overview of IKBKG/NEMO mutations in EDA-ID and IP patients and describe similarities and differences between the clinical/immunophenotypic and genetic aspects, highlighting any T and B lymphocyte defect, and paying particular attention to the cellular and molecular defects that underlie the pathogenesis of both diseases

Masterprojekt Zweitwohnsitz im alpinen Raum. Gesamtbericht WS 2020/21

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