The role of the NadR regulator during infection and its implication for the coverage of a new Meningococcus B vaccine

Background: Neisseria meningitides represents a major cause of meningitis and sepsis. The meningococcal regulator NadR was previously shown to repress the expression of the Neisserial Adhesin A (NadA) and play a major role in its phase-variation. NadA is a surface exposed protein involved in epithelial cell adhesion and colonization and a major component of 4CMenB, a novel vaccine to prevent meningococcus serogroup B infection. The NadR mediated repression of NadA is attenuated by 4-HPA, a natural molecule released in human saliva. Results: In this thesis we investigated the global role of NadR during meningogoccal infection, identifying through microarray analysis the NadR regulon. Two distinct types of NadR targets were identified, differing in their promoter architectures and 4HPA responsive activities: type I are induced, while type II are co-repressed in response to the same 4HPA signal. We then investigate the mechanism of regulation of NadR by 4-HPA, generating NadR mutants and identifying classes or residues involved in either NadR DNA binding or 4HPA responsive activities. Finally, we studied the impact of NadR mediated repression of NadA on the vaccine coverage of 4CMenB. A selected MenB strains is not killed by sera from immunized infants when the strain is grown in vitro, however, in an in vivo passive protection model, the same sera protected infant rats from bacteremia. Finally, using bioluminescent reporters, nadA expression in the infant rat model was induced in vivo at 3 h post-infection. Conclusions: Our results suggest that NadR coordinates a broad transcriptional response to signals present in the human host, enabling the meningococcus to adapt to the relevant host niche. During infectious disease the effect of the same signal on NadR changes between different targets. In particular NadA expression is induced in vivo, leading to efficient killing of meningococcus by anti-NadA antibodies elicited by the 4CMenB vaccine.

Efficient wireless coverage of in-building environments with low electromagnetic impact

The city of tomorrow is a major integrating stake, which crosses a set of major broad spectrum domains. One of these areas is the instrumentation of this city and the ubiquity of the exchange of data, which will give the pulse of this city (sensors) and its breathing in a hyper-connected world within indoor and outdoor dense areas (data exchange, 5G and 6G). Within this context, the proposed doctorate project has the objective to realize cost- and energy- effective, short-range communication systems for the capillary wireless coverage of in-door environments with low electromagnetic impact and for highly dense outdoor networks. The result will be reached through the combined use of: 1) Radio over Fiber (RoF) Technology, to bring the Radio Frequency (RF) signal to the different areas to be covered. 2) Beamforming antennas to send in real time the RF power just in the direction(s) where it is really necessary.

Diversified applications of supplemental LED light for greenhouse tomato production in the Mediterranean context

Among the various aspects to be investigated for a technological and productive upgrade of tomato greenhouse production in the Mediterranean area, the application of supplementary LED interlighting still shows limited interest. However, high-density tomato cultivation with intensive high-wire systems could lead to mutual shading and consequent reduction in photosynthesis and yield, even in case of appreciable amounts of external solar radiation, as in Southern Europe. Applications of interest could also involve off-season production or Building-Integrated Agriculture (BIA) such as rooftop greenhouses, where municipal regulations for structure and fire safety could limit the incoming radiation in the growing area. The aim of this research was to investigate diversified applications of supplemental LED interlighting for greenhouse tomato production (Solanum lycopersicum) in the Mediterranean countries. The diversified applications included: effects on post-harvest quality, shading reduction in BIA, tailored seedlings production, and off-season cultivation. The results showed that the application of supplemental LED light on greenhouse-grown tomato in Mediterranean countries (Italy and Spain) has potential to foster diverse applications. In particular, it can increase production in case of the limited solar radiation in rooftop greenhouses, maintain quality and reduce losses during post-harvest, help producing high quality and tailored seedlings, and increase yield during wintertime. Despite the positive results obtained, some aspects of the application of additional LED light in Southern Europe countries still need to be deepened and improved. In particular, given the current increase of electricity cost, future research should focus on more economically valuable methods of managing supplemental lighting, such as the application of shorter photoperiods or lower intensities, or techniques that can provide energy savings such as the pulsed light.