Reconstruction and analysis of the NF-kB pathway interactome: a systems biology approach

Background. One of the phenomena observed in human aging is the progressive increase of a systemic inflammatory state, a condition referred to as “inflammaging”, negatively correlated with longevity. A prominent mediator of inflammation is the transcription factor NF-kB, that acts as key transcriptional regulator of many genes coding for pro-inflammatory cytokines. Many different signaling pathways activated by very diverse stimuli converge on NF-kB, resulting in a regulatory network characterized by high complexity. NF-kB signaling has been proposed to be responsible of inflammaging. Scope of this analysis is to provide a wider, systemic picture of such intricate signaling and interaction network: the NF-kB pathway interactome. Methods. The study has been carried out following a workflow for gathering information from literature as well as from several pathway and protein interactions databases, and for integrating and analyzing existing data and the relative reconstructed representations by using the available computational tools. Strong manual intervention has been necessarily used to integrate data from multiple sources into mathematically analyzable networks. The reconstruction of the NF-kB interactome pursued with this approach provides a starting point for a general view of the architecture and for a deeper analysis and understanding of this complex regulatory system. Results. A “core” and a “wider” NF-kB pathway interactome, consisting of 140 and 3146 proteins respectively, were reconstructed and analyzed through a mathematical, graph-theoretical approach. Among other interesting features, the topological characterization of the interactomes shows that a relevant number of interacting proteins are in turn products of genes that are controlled and regulated in their expression exactly by NF-kB transcription factors. These “feedback loops”, not always well-known, deserve deeper investigation since they may have a role in tuning the response and the output consequent to NF-kB pathway initiation, in regulating the intensity of the response, or its homeostasis and balance in order to make the functioning of such critical system more robust and reliable. This integrated view allows to shed light on the functional structure and on some of the crucial nodes of thet NF-kB transcription factors interactome. Conclusion. Framing structure and dynamics of the NF-kB interactome into a wider, systemic picture would be a significant step toward a better understanding of how NF-kB globally regulates diverse gene programs and phenotypes. This study represents a step towards a more complete and integrated view of the NF-kB signaling system.

Functional photoactive and electroactive nanodevices

Most of current ultra-miniaturized devices are obtained by the top-down approach, in which nanoscale components are fabricated by cutting down larger precursors. Since this physical-engineering method is reaching its limits, especially for components below 30 nm in size, alternative strategies are necessary. Of particular appeal to chemists is the supramolecular bottom-up approach to nanotechnology, a methodology that utilizes the principles of molecular recognition to build materials and devices from molecular components. The subject of this thesis is the photophysical and electrochemical investigation of nanodevices obtained harnessing the principles of supramolecular chemistry. These systems operate in solution-based environments and are investigated at the ensemble level. The majority of the chemical systems discussed here are based on pseudorotaxanes and catenanes. Such supramolecular systems represent prototypes of molecular machines since they are capable of performing simple controlled mechanical movements. Their properties and operation are strictly related to the supramolecular interactions between molecular components (generally photoactive or electroactive molecules) and to the possibility of modulating such interactions by means of external stimuli. The main issues addressed throughout the thesis are: (i) the analysis of the factors that can affect the architecture and perturb the stability of supramolecular systems; (ii) the possibility of controlling the direction of supramolecular motions exploiting the molecular information content; (iii) the development of switchable supramolecular polymers starting from simple host-guest complexes; (iv) the capability of some molecular machines to process information at molecular level, thus behaving as logic devices; (v) the behaviour of molecular machine components in a biological-type environment; (vi) the study of chemically functionalized metal nanoparticles by second harmonic generation spectroscopy.

The school environment as a teacher. The role of space and place in enhancing ecological literacy and social competence development in children and young people

Can space and place foster child development, and in particular social competence and ecological literacy? If yes, how can space and place do that? This study shows that the answer to the first question is positive and then tries to explain the way space and place can make a difference. The thesis begins with the review of literature from different disciplines – child development and child psychology, education, environmental psychology, architecture and landscape architecture. Some bridges among such disciplines are created and in some cases the ideas from the different areas of research merge: thus, this is an interdisciplinary study. The interdisciplinary knowledge from these disciplines is translated into a range of design suggestions that can foster the development of social competence and ecological literacy. Using scientific knowledge from different disciplines is a way of introducing forms of evidence into the development of design criteria. However, the definition of design criteria also has to pass through the study of a series of school buildings and un-built projects: case studies can give a positive contribution to the criteria because examples and good practices can help “translating” the theoretical knowledge into design ideas and illustrations. To do that, the different case studies have to be assessed in relation to the various themes that emerged in the literature review. Finally, research by design can be used to help define the illustrated design criteria: based on all the background knowledge that has been built, the role of the architect is to provide a series of different design solutions that can give answers to the different “questions” emerged in the literature review.

Genetic basis of variation for root traits and response to heat stress in durum wheat

Durum wheat is the second most important wheat species worldwide and the most important crop in several Mediterranean countries including Italy. Durum wheat is primarily grown under rainfed conditions where episodes of drought and heat stress are major factors limiting grain yield. The research presented in this thesis aimed at the identification of traits and genes that underlie root system architecture (RSA) and tolerance to heat stress in durum wheat, in order to eventually contribute to the genetic improvement of this species. In the first two experiments we aimed at the identification of QTLs for root trait architecture at the seedling level by studying a bi-parental population of 176 recombinant inbred lines (from the cross Meridiano x Claudio) and a collection of 183 durum elite accessions. Forty-eight novel QTLs for RSA traits were identified in each of the two experiments, by means of linkage- and association mapping-based QTL analysis, respectively. Important QTLs controlling the angle of root growth in the seedling were identified. In a third experiment, we investigated the phenotypic variation of root anatomical traits by means of microscope-based analysis of root cross sections in 10 elite durum cultivars. The results showed the presence of sizeable genetic variation in aerenchyma-related traits, prompting for additional studies aimed at mapping the QTLs governing such variation and to test the role of aerenchyma in the adaptive response to abiotic stresses. In the fourth experiment, an association mapping experiment for cell membrane stability at the seedling stage (as a proxy trait for heat tolerance) was carried out by means of association mapping. A total of 34 QTLs (including five major ones), were detected. Our study provides information on QTLs for root architecture and heat tolerance which could potentially be considered in durum wheat breeding programs.