Towards an integrated evaluation approach for cultural urban landscape conservation/regeneration

The contemporary economic crisis (and also ecological and social crisis) calls for a new model of urban development. The international debate is today focused on the necessity of a new paradigm (Hosagrahar et al., 2016) that will define sustainable development policies and programmes: this new paradigm moves the concept of development towards a more humanistic and ecological point of view. The international debate around Sustainable Development Goals (SDGs) recently is going to highlight the role of cultural heritage for sustainable development (United Nations, 2015a). Cultural heritage can play a critical role in the achievement of the above mentioned new humanistic and ecological paradigm of sustainable city. In this paper some indicators to evaluate cultural urban landscape conservation/regeneration projects are identified, starting from case studies. The purpose of the analysis of good practices is to support the elaboration of a multidimensional matrix that can produce empirical evidence about impacts of cultural urban landscape conservation/regeneration. After a particular focus on the relationship between variation of landscape and variation of wellbeing, it will present a methodological proposal to evaluate cultural urban landscape conservation/regeneration projects

Hybrid evaluation tools for operationalizing UNESCO Historic Urban Landscape Approach

The present research is part of the international debate about the role of cities in the achievement of sustainable development. The thesis stresses the role of cities and human settlements to shape the implementation of Sustainable Development Goals (SDGs) in an increasingly urbanized world. It aims to make operational concepts driving sustainable transformations of cities and territories in the evaluation field. Its purpose is to put into operational terms concepts and categories identified by international organizations, otherwise at risk of being confined to a purely abstract reflections. The thesis aims to provide an evaluation approach and a multidimensional indicators matrix for supporting the valorization/regeneration projects/management strategies of cities and territory, conscious that the Historic Urban Landscape conservation does not represents a cost, but an investment able to increase the city multidimensional productivity. The present thesis mainly focuses the attention on the historic port cities because of their peculiar characteristics. After an overview of the actual international debate about sustainable development, the recognition of the role of cultural heritage/landscape in sustainable development is analysed through the examination of international conferences and documents, with particular reference to 2030 Agenda for Sustainable Development (United Nation, 2015) and The New Urban Agenda (United Nation, 2016a). The UNESCO Historic Urban Landscape approach (HUL) (UNESCO, 2011), the latest contribution of the international debate on the identification, conservation and enhancement of cultural heritage, is analysed in depth. The notion of urban heritage is inseparable from its multidimensional nature, so it requires an “inclusive approach” able to include the dynamic dimension of cultural landscape and its multiple values/dimensions. In the perspective of Historic Urban Landscape, an operational indicators matrix has proposed for evaluating the multidimensional impacts of conservation/regeneration projects, that is for producing empirical evidence about multidimensional benefits of cultural landscape conservation/regeneration. The set of proposed multidimensional indicators is deduced from the analysis of about 40 good practices of conservation/regeneration projects. The impacts analysed, both on cultural heritage and from cultural heritage, are classified in 9 impact categories. In the present research, transformation processes of cities are placed into a new framework, the circular economy. The circular model, based on principles characterizing natural ecosystems (based on circular processes where nothing is “waste” and everything can become a “resource”), is proposed to operationalize sustainable development principles. It is not only referred to waste cycle (European Commission, 2015), but it is the economy of synergies and symbiosis between different industrial activities, city and industrial system, etc. and offers great opportunities to increase urban productivity. The highlighted multidimensional perspective of cities transformation implies a systemic and integrated approach that requires new assessment tools. Economic approach is necessary, but it is not sufficient. It needs an integrated evaluation tool, in which quantitative economic matrix is enriched with qualitative indicators, expressed by social components (social matrix) and environmental components (ecological matrix). The thesis does not intend to propose a new evaluation method, but rather an evaluation process, capitalizing the richness of existing tools. It aims to provide a tool for supporting decision-makers in the evaluation of impacts of projects at different scale. An operational approach is proposed for the assessment of the impacts on and from cultural heritage conservation/regeneration projects. The case study of Pozzuoli (Italy) represents a concrete implementation of the proposed methodology, demonstrating its application potentialities. It represents a good opportunity to concretely put into practice the issues discussed because it is characterized by a valuable cultural and natural landscape and a complex city-port system. Considering the multidimensionality of the impacts, multi-group and multi-criteria analysis are processed to evaluate the more appropriate combination of functions to valorize the area and the resources of the territory; in other words, to increase city productivity. The proposed methodological approach, starting from the multidimensional indicators matrix, is applied in the case study in order to include multiple dimensions in the evaluation process, supporting the identification of sustainable development strategies. This evaluation approach takes into account the above highlighted multidimensionality, also including both expert and community knowledge. The proposed evaluation approach and the multidimensional indicators matrix aim to provide a valuable tool for supporting city regeneration/valorization projects/management strategies, aware that the Historic Urban Landscape conservation is an investment able to increase multidimensional productivity of cities, and not a cost. This research intends to provide an operational approach to support decision-makers to orient and assess choices addressed to the achievement (and the increase) of multidimensional productivity of cities. The set of indicators can represent a general indicator framework that can be used to evaluate cultural landscape impacts in different territorial situation, but contextualizing it case by case. The choice of key indicators to be considered depends on the aims of the projects, the location and scale of intervention (building, site, etc.). The proposed indicators matrix can be used both for ex-ante and ex-post assessment

SUMO-1 regulates the conformational dynamics of Thymine-DNA Glycosylase regulatory domain and competes with its DNA binding activity

<p>Abstract</p> <p>Background</p> <p>The human thymine-DNA glycosylase (TDG) plays a dual role in base excision repair of G:U/T mismatches and in transcription. Regulation of TDG activity by SUMO-1 conjugation was shown to act on both functions. Furthermore, TDG can interact with SUMO-1 in a non-covalent manner.</p> <p>Results</p> <p>Using NMR spectroscopy we have determined distinct conformational changes in TDG upon either covalent sumoylation on lysine 330 or intermolecular SUMO-1 binding through a unique SUMO-binding motif (SBM) localized in the C-terminal region of TDG. The non-covalent SUMO-1 binding induces a conformational change of the TDG amino-terminal regulatory domain (RD). Such conformational dynamics do not exist with covalent SUMO-1 attachment and could potentially play a broader role in the regulation of TDG functions for instance during transcription. Both covalent and non-covalent processes activate TDG G:U repair similarly. Surprisingly, despite a dissociation of the SBM/SUMO-1 complex in presence of a DNA substrate, SUMO-1 preserves its ability to stimulate TDG activity indicating that the non-covalent interactions are not directly involved in the regulation of TDG activity. SUMO-1 instead acts, as demonstrated here, indirectly by competing with the regulatory domain of TDG for DNA binding.</p> <p>Conclusions</p> <p>SUMO-1 increases the enzymatic turnover of TDG by overcoming the product-inhibition of TDG on apurinic sites. The mechanism involves a competitive DNA binding activity of SUMO-1 towards the regulatory domain of TDG. This mechanism might be a general feature of SUMO-1 regulation of other DNA-bound factors such as transcription regulatory proteins.</p

From linear to circular tourism

Tourism is the third largest socio-economic activity in the EU and thus it can be considered an engine for development, producing many positive impacts, from trade sector to employment. At the same time, it can produce many negative impacts because it is configured according to the model of linear economy. A deep analysis of impacts produced by tourism sector and its great potential in contributing to the achievement of SDGs are presented. The aim of this paper is to identify a tourism development/management model able to produce multidimensional benefits and, simultaneously, reduce (environmental, social and economic) costs. In this perspective, the circular economy is proposed as a model able to contribute to make tourism more sustainable. This model necessarily requires appropriate evaluation tools, indicators and knowledge.Tourism is the third largest socio-economic activity in the EU and thus it can be considered an engine for development, producing many positive impacts, from trade sector to employment. At the same time, it can produce many negative impacts because it is configured according to the model of linear economy. A deep analysis of impacts produced by tourism sector and its great potential in contributing to the achievement of SDGs are presented. The aim of this paper is to identify a tourism development/management model able to produce multidimensional benefits and, simultaneously, reduce (environmental, social and economic) costs. In this perspective, the circular economy is proposed as a model able to contribute to make tourism more sustainable. This model necessarily requires appropriate evaluation tools, indicators and knowledge

Is It Safe to Combine a Fundoplication to Sleeve Gastrectomy? Review of Literature

Complicacions; Fundoplicatura; MànigaComplicaciones; Funduplicatura; MangaComplications; Fundoplication; SleeveBackground and Objectives: The rising numbers of laparoscopic sleeve gastrectomy (LSG) procedures now being performed worldwide will likely be followed by an increasing number of patients experiencing gastro-esophageal reflux disease (GERD). The purpose of the current review was to analyze in terms of safety different techniques of fundoplication used to treat GERD associated with LSG. Methods: An online search was performed in PubMed/MEDLINE in December 2020 to identify articles reporting LSG and fundoplication. The following term combination was used: (sleeve, fundoplication), (sleeve, Nissen), (sleeve, Rossetti), (sleeve, Toupet) and (sleeve, Dor). The extracted information included details of the methods (e.g., retrospective case series), demographic characteristics (e.g., age, gender), clinical characteristics, number of patients, rate of conversion, and postoperative outcomes. Results: A total of 154 studies were identified and after an assessment of title according to our exclusion criteria, 116 articles were removed. Of the 38 studies analyzed for full content review, a total of seven primary studies (487 patients) were identified with all inclusion criteria. Analyzing the different types of fundoplication used, we have identified: 236 cases of Nissen-Sleeve, 220 cases with modified Rossetti fundoplication, 31 cases of Dor fundoplication, and no case of Toupet fundoplication. The overall postoperative complication rate was 9.4%, with the most common reported complication being gastric perforation, 15 cases—3.1%. The second most common complication was bleeding identified in nine cases (1.8%) followed by gastric stenosis in six cases (1.2%). The mortality was nil. Conclusions: Different types of fundoplication associated with LSG appear to be a safe surgical technique with an acceptable early postoperative complication rate. Any type of fundoplication associated with LSG to decrease GERD should be evaluated cautiously while prospective clinical randomized trials are needed.This research received no external funding

Phosphorylation and O-GlcNAcylation of the PHF-1 Epitope of Tau Protein Induce Local Conformational Changes of the C-Terminus and Modulate Tau Self-Assembly Into Fibrillar Aggregates

Phosphorylation of the neuronal microtubule-associated Tau protein plays a critical role in the aggregation process leading to the formation of insoluble intraneuronal fibrils within Alzheimer’s disease (AD) brains. In recent years, other posttranslational modifications (PTMs) have been highlighted in the regulation of Tau (dys)functions. Among these PTMs, the O-β-linked N-acetylglucosaminylation (O-GlcNAcylation) modulates Tau phosphorylation and aggregation. We here focus on the role of the PHF-1 phospho-epitope of Tau C-terminal domain that is hyperphosphorylated in AD (at pS396/pS404) and encompasses S400 as the major O-GlcNAc site of Tau while two additional O-GlcNAc sites were found in the extreme C-terminus at S412 and S413. Using high resolution NMR spectroscopy, we showed that the O-GlcNAc glycosylation reduces phosphorylation of PHF-1 epitope by GSK3β alone or after priming by CDK2/cyclin A. Furthermore, investigations of the impact of PTMs on local conformation performed in small peptides highlight the role of S404 phosphorylation in inducing helical propensity in the region downstream pS404 that is exacerbated by other phosphorylations of PHF-1 epitope at S396 and S400, or O-GlcNAcylation of S400. Finally, the role of phosphorylation and O-GlcNAcylation of PHF-1 epitope was probed in in-vitro fibrillization assays in which O-GlcNAcylation slows down the rate of fibrillar assembly while GSK3β phosphorylation stimulates aggregation counteracting the effect of glycosylation.Peer Reviewe

SUMO-1 possesses DNA binding activity

<p>Abstract</p> <p>Background</p> <p>Conjugation of small ubiquitin-related modifiers (SUMOs) is a frequent post-translational modification of proteins. SUMOs can also temporally associate with protein-targets via SUMO binding motifs (SBMs). Protein sumoylation has been identified as an important regulatory mechanism especially in the regulation of transcription and the maintenance of genome stability. The precise molecular mechanisms by which SUMO conjugation and association act are, however, not understood.</p> <p>Findings</p> <p>Using NMR spectroscopy and protein-DNA cross-linking experiments, we demonstrate here that SUMO-1 can specifically interact with dsDNA in a sequence-independent fashion. We also show that SUMO-1 binding to DNA can compete with other protein-DNA interactions at the example of the regulatory domain of Thymine-DNA Glycosylase and, based on these competition studies, estimate the DNA binding constant of SUMO1 in the range 1 mM.</p> <p>Conclusion</p> <p>This finding provides an important insight into how SUMO-1 might exert its activity. SUMO-1 might play a general role in destabilizing DNA bound protein complexes thereby operating in a bottle-opener way of fashion, explaining its pivotal role in regulating the activity of many central transcription and DNA repair complexes.</p

In vitro Evaluation of the Cytotoxicity of Different Root Canal Filling Materials

Objective: Aim of the present study was to evaluate the cytotoxicity of Real Seal 1 compared to other commercially available endodontic filling materials: Real Seal (SybronEndo, Orange, CA, USA) and Thermafil (Tulsa Dental, Tulsa, OK, USA). Material and Methods: Periodontal ligament cells from healthy patients were cultured. The eluate of Real Seal 1TM (RS1), Real Seal (RS) and Thermafil (TF) samples was used for the cells viability tests, both diluted (50%) or undiluted (100%). Incubation of the specimens was performed in culture medium for 24 h, 48 h and 72 h at 37 °C under sterile conditions. The cellular mortality was evaluated by MTT test. Results were statistically analysed and the statistical significance was set at p&lt; 0.05. Results: None of the studied materials showed toxic effects during the period of observation (0 -72 h) when compared to the control group. Only RS induced a very modest increase in cell mortality (about 3% at both concentrations used, during the first 24 hours), when increasing the incubation time, however, only the lower concentration continued to show modest toxicity. Conclusions: Results of the present study showed that all tested materials did not exhibit cytotoxic effects when compared to the control group. © Gambarini et al

Cinnamaldehyde Loaded poly(lactide-co-glycolide) (PLGA) Microparticles for Antifungal Delivery Application against Resistant Candida albicans and Candida glabrata

Researchers have explored natural products to combat the antibiotic resistance of various microorganisms. Cinnamaldehyde (CIN), a major component of cinnamon essential oil (CC-EO), has been found to effectively inhibit the growth of bacteria, fungi, and mildew, as well as their production of toxins. Therefore, this study aimed to create a delivery system for CIN using PLGA microparticles (CIN-MPs), and to compare the antifungal activity of the carried and free CIN, particularly against antibiotic-resistant strains of Candida spp. The first part of the study focused on synthesizing and characterizing the PLGA MPs, which had no toxic effects in vivo and produced results in line with the existing literature. The subsequent experiments analyzed the antifungal effects of MPs-CIN on Candida albicans and Candida glabrata, both resistant (R) and sensitive (S) strains and compared its efficacy with the conventional addition of free CIN to the culture medium. The results indicated that conveyed CIN increased the antifungal effects of the product, particularly towards C. albicans R. The slow and prolonged release of CIN from the PLGA MPs ensured a constant and uniform concentration of the active principle within the cell