Diet Effects on Activation and Maturation of Feed Control over the Gastrointestinal Defence Barrier in Piglets

Weaning is an important and complex step involving many stresses that interfere deeply with feed intake, gastro-intestinal tract (GIT) development and adaptation to the weaning diet in young pigs. The health of the pig at weaning, its nutrition in the immediate post-weaning period, and the physical, microbiological and psychological environment are all factors that interact to determine food intake and subsequent growth. GIT disorders, infections and diarrhoea increase at the time of weaning, in fact pathogens such as enterotoxigenic Escherichia coli (ETEC) are major causes of mucosal damage in post-weaning disease contributing to diarrhoea in suckling and post-weaned pigs. The European ban in 2006 put on antibiotic growth promoters (AGP) has stimulated research on the mechanisms of GIT disorders and on nutritional approaches for preventing or reducing such disturbances avoiding AGPs. Concerning these aspects here are presented five studies based on the interplay among nutrition, genomic, immunity and physiology with the aim to clarify some of these problematic issues around weaning period in piglets. The first three evaluate the effects of diets threonine or tryptophan enriched on gut defence and health as possible alternatives to AGP in the gut. The fourth is focused on the possible immunological function related with the development of the stomach. The fifth is a pilot study on the gastric sensing and orexygenic signal given by fasting or re-feeding conditions. Although some results are controversial, it appears that both tryptophan and threonine supplementation in weaning diets have a preventive role in E.coli PWD and favorable effects in the gut especially in relation to ETEC susceptible genotype. While the stomach is believed as almost aseptic organ, it shows an immune activity related with the mucosal maturation. Moreover it shows an orexygenic role of both oxyntic mucosa and pyloric mucosa, and its possible relation with nutrient sensing stimuli.

Development Aid to Water Management in Mali: The Actors, ‘Global’ Paradigms, and ‘Local’ Translations

Development aid involves a complex network of numerous and extremely heterogeneous actors. Nevertheless, all actors seem to speak the same ‘development jargon’ and to display a congruence that extends from the donor over the professional consultant to the village chief. And although the ideas about what counts as ‘good’ and ‘bad’ aid have constantly changed over time —with new paradigms and policies sprouting every few years— the apparent congruence between actors more or less remains unchanged. How can this be explained? Is it a strategy of all actors to get into the pocket of the donor, or are the social dynamics in development aid more complex? When a new development paradigm appears, where does it come from and how does it gain support? Is this support really homogeneous? To answer the questions, a multi-sited ethnography was conducted in the sector of water-related development aid, with a focus on 3 paradigms that are currently hegemonic in this sector: Integrated Water Resources Management, Capacity Building, and Adaptation to Climate Change. The sites of inquiry were: the headquarters of a multilateral organization, the headquarters of a development NGO, and the Inner Niger Delta in Mali. The research shows that paradigm shifts do not happen overnight but that new paradigms have long lines of descent. Moreover, they require a lot of work from actors in order to become hegemonic; the actors need to create a tight network of support. Each actor, however, interprets the paradigms in a slightly different way, depending on the position in the network. They implant their own interests in their interpretation of the paradigm (the actors ‘translate’ their interests), regardless of whether they constitute the donor, a mediator, or the aid recipient. These translations are necessary to cement and reproduce the network.

Comparing genetic and linguistic diversity in African populations with a focus on the Khoisan of southern Africa

The interaction between disciplines in the study of human population history is of primary importance, profiting from the biological and cultural characteristics of humankind. In fact, data from genetics, linguistics, archaeology and cultural anthropology can be combined to allow for a broader research perspective. This multidisciplinary approach is here applied to the study of the prehistory of sub-Saharan African populations: in this continent, where Homo sapiens originally started his evolution and diversification, the understanding of the patterns of human variation has a crucial relevance. For this dissertation, molecular data is interpreted and complemented with a major contribution from linguistics: linguistic data are compared to the genetic data and the research questions are contextualized within a linguistic perspective. In the four articles proposed, we analyze Y chromosome SNPs and STRs profiles and full mtDNA genomes on a representative number of samples to investigate key questions of African human variability. Some of these questions address i) the amount of genetic variation on a continental scale and the effects of the widespread migration of Bantu speakers, ii) the extent of ancient population structure, which has been lost in present day populations, iii) the colonization of the southern edge of the continent together with the degree of population contact/replacement, and iv) the prehistory of the diverse Khoisan ethnolinguistic groups, who were traditionally understudied despite representing one of the most ancient divergences of modern human phylogeny. Our results uncover a deep level of genetic structure within the continent and a multilayered pattern of contact between populations. These case studies represent a valuable contribution to the debate on our prehistory and open up further research threads.

Numerical and Analytical Methods for Laser-Plasma Acceleration Physics

Theories and numerical modeling are fundamental tools for understanding, optimizing and designing present and future laser-plasma accelerators (LPAs). Laser evolution and plasma wave excitation in a LPA driven by a weakly relativistically intense, short-pulse laser propagating in a preformed parabolic plasma channel, is studied analytically in 3D including the effects of pulse steepening and energy depletion. At higher laser intensities, the process of electron self-injection in the nonlinear bubble wake regime is studied by means of fully self-consistent Particle-in-Cell simulations. Considering a non-evolving laser driver propagating with a prescribed velocity, the geometrical properties of the non-evolving bubble wake are studied. For a range of parameters of interest for laser plasma acceleration, The dependence of the threshold for self-injection in the non-evolving wake on laser intensity and wake velocity is characterized. Due to the nonlinear and complex nature of the Physics involved, computationally challenging numerical simulations are required to model laser-plasma accelerators operating at relativistic laser intensities. The numerical and computational optimizations, that combined in the codes INF&RNO and INF&RNO/quasi-static give the possibility to accurately model multi-GeV laser wakefield acceleration stages with present supercomputing architectures, are discussed. The PIC code jasmine, capable of efficiently running laser-plasma simulations on Graphics Processing Units (GPUs) clusters, is presented. GPUs deliver exceptional performance to PIC codes, but the core algorithms had to be redesigned for satisfying the constraints imposed by the intrinsic parallelism of the architecture. The simulation campaigns, run with the code jasmine for modeling the recent LPA experiments with the INFN-FLAME and CNR-ILIL laser systems, are also presented.

The impact of intraclonal heterogeneity on the outcomes of Multiple Myeloma patients treated with new drugs

Understanding the biology of Multiple Myeloma (MM) is of primary importance in the struggle to achieve a cure for this yet incurable neoplasm. A better knowledge of the mechanism underlying the development of MM can guide us in the development of new treatment strategies. Studies both on solid and haematological tumours have shown that cancer comprises a collection of related but subtly different clones, a feature that has been termed “intra-clonal heterogeneity”. This intra-clonal heterogeneity is likely, from a “Darwinian” natural selection perspective, to be the essential substrate for cancer evolution, disease progression and relapse. In this context the critical mechanism for tumour progression is competition between individual clones (and cancer stem cells) for the same microenvironmental “niche”, combined with the process of adaptation and natural selection. The Darwinian behavioural characteristics of cancer stem cells are applicable to MM. The knowledge that intra-clonal heterogeneity is an important feature of tumours’ biology has changed our way to addressing cancer, now considered as a composite mixture of clones and not as a linear evolving disease. In this variable therapeutic landscape it is important for clinicians and researchers to consider the impact that evolutionary biology and intra-clonal heterogeneity have on the treatment of myeloma and the emergence of treatment resistance. It is clear that if we want to effectively cure myeloma it is of primarily importance to understand disease biology and evolution. Only by doing so will we be able to effectively use all of the new tools we have at our disposal to cure myeloma and to use treatment in the most effective way possible. The aim of the present research project was to investigate at different levels the presence of intra-clonal heterogeneity in MM patients, and to evaluate the impact of treatment on clonal evolution and on patients’ outcomes.