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Biodiversity and ecosystems dynamics of rangelands on a climatic gradient in face of management and desertification threats
No full textBioaccumulation and bioremediation modelling in Aquatic ecosystems: the Adriatic Sea case study
No full textUnderstanding the pathways of contaminant transfer within trophic networks is of paramount importance to weigh up forces driving ecological changes and to plan focused intervention strategies targeted to environmental\ud
conservation. The subject developed in this PhD dissertation aligns with this goal and encompasses the combination of different modelling approaches with experimental data to interpret the effects of bioaccumulation and bioremediation phenomena on species.\ud
Toxic agents adversely influence substance and energy fluxes at the ecosystem level affecting in turn the number of inter- and intra-specific interactions\ud
both at the community and population levels. Furthermore, the environmental stochasticity and the diversity of food webs along with the specificity of action of different bioaccumulative compounds greatly increase the\ud
complexity of this field of research. Current challenges in ecotoxicology focus on the need to find reliable predictive tools able to turn toxicity data of biota into powerful estimation methods and to asses the long-term effects of chemical exposure on species.\ud
In this context, predator-prey relationships are crucial to characterize the contamination patterns and to predict how chemicals transfer and accumulate within food webs. Food web members exhibit different levels of bioaccumulation in function of their trophic role, in a way that trophic links cannot be considered equal for all species in bioaccumulation phenomena.\ud
However, marine ecosystems are not just ensembles of macro-species, but complex multiscale networks. Microbial marine communities are metabolically involved in bioremediation processes and also represent an active compartment in the lower trophic levels of food webs. Thus, microbial degradation of persistent organic chemicals may play a key factor in changing the fate of these compounds within ecosystems and in reducing the contaminant uptake that leads to bioaccumulation in marine species.\ud
The work of research carried out during my PhD studies has been centred on the bioaccumulation and bioremediation modelling problems with specific interest on polychlorinated biphenyls (PCBs) contamination of the\ud
Adriatic food web. Notwithstanding a number of specific experimental studies on PCBs concentrations in different Adriatic species have been carried out over the last decades, to the best of our knowledge, a comprehensive\ud
PCBs bioaccumulation model for the Adriatic food web was still missing prior to the work presented in this thesis.\ud
The contributions of this PhD dissertation are structured by publication.\ud
Chapter 1 introduces the main content and includes an unpublished review of experimental PCBs concentration data in Adriatic species over the last two decades, along with an overview of the most important modelling approaches for bioaccumulation and bioremediation.\ud
In Chapter 2, we present a computational framework to model the bioaccumulation of organic chemicals in aquatic food webs, and to discover the toxic keystones, i.e. the species with a key role in the trophic transfer of\ud
contaminants. The approach is applied to reconstruct the first PCBs bioaccumulation model of the Adriatic food web, parametrized with a subset of the concentration data reviewed in Chapter 1. The framework integrates\ud
different modelling and analysis techniques, the first being the reconstruction of a trophic network from biomass data. Then, we use the estimated biomass flows and concentration data to derive the PCBs bioaccumulation\ud
network. Network reconstruction is performed using linear inverse modelling (LIM), an efficient technique for estimating food webs from empirical data. This step allows us to infer concentration values and contaminant\ud
flows for all species and remarkably, also for species with no input data associated. The estimated concentrations highlight the occurrence of PCBs\ud
biomagnification, which we show depending mainly on the trophic structure. The second main part of the framework is dedicated to the problem of identifying the toxic keystones, for which we propose the application of\ud
network analysis tools, typically employed in the trophic context. To this aim, we define a new network index, sensitivity centrality, able to capture not just direct and indirect effects in the PCBs network, but also the dynamics of bioaccumulation. Indeed, the index is based on the sensitivity analysis of a differential equation model derived from the bioaccumulation network. We compare sensitivity centrality with established network centrality indices, by evaluating the impact of successive species extinctions on global network properties, where such extinctions are performed following the importance ordering of the different indices. This analysis demonstrates that the introduced index can better identify the species with the highest impact on the total contaminant flows and on the efficiency of contaminant transport within the food web.\ud
In Chapter 3, we propose a novel computational framework of analysis to investigate multiscale effects of bioremediation processes at the ecosystem level. We integrate the bioaccumulation model presented in Chapter\ud
2 with the genome-scale metabolic network of Pseudomonas putida KT2440 (iJN746), which we extend to simulate the aerobic PCBs degradation under arbitrary scenarios of contaminant removal. We use a reaction-based ecological/microbial network representation by combining ecological and metabolic modelling techniques, namely LIM and flux balance analysis. In this way, we describe in a unique framework PCBs flows among species, metabolites concentrations and reactions fluxes in the microbial metabolism. We investigate the tradeoff between PCBs uptake and growth of P. putida at different oxygen levels, by using a bi-level flux balance analysis approach. We study the interdependence between PCBs and toluene uptake, which is a natural degradation pathways in P. putida, by performing a phenotypic phase plane analysis. We apply this framework to study how different\ud
bioremediation strategies can impact PCBs concentration in species, thus enabling an ecosystem level analysis. Finally, we evaluate also the effect of bioremediation on indices of species centrality in the PCBs bioaccumulation\ud
network.\ud
To sum up, the aims and contributions of this PhD thesis are:\ud
Provide a review of PCBs concentration data in the Adriatic ecosystem and of modelling methods for bioaccumulation and bioremediation.\ud
Reconstruct the first PCBs bioaccumulation model of the Adriatic food web and investigate species having a central role in the trophic transfer of contaminants.\ud
Integrate the Adriatic bioaccumulation model with a genome-scale metabolic model for PCBs biodegradation in order to enable multiscale ecosystem analyses.\ud
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References\ud
chapter 2: M. Taffi, N. Paoletti, P. Liò, S. Pucciarelli, and M. Marini. Bioaccumulation modelling and sensitivity analysis for discovering key players in contaminated food\ud
webs: The case study of PCBs in the Adriatic Sea. Ecological Modelling, 2014.\ud
chapter 3: M. Taffi, N. Paoletti, C. Angione, S. Pucciarelli, M. Marini, and P. Liò. Bioremediation\ud
in marine ecosystems: a computational study combining ecological modelling and flux balance analysis. Frontiers in Genetics, 5(319), 2014.\ud
Identification of two new small ncRNAs, 3' and 5' Glu-tRNA-derived fragments: their possible role as biomarkers for breast cancer\ud PhD
No full textOver the last decades, small non-coding RNAs (ncRNAs), ~13-40 nucleotides long, have been discovered. Many classes of this kind of molecules have been described: microRNAs (miRNAs), small interfering RNAs (siRNAs) and piwi-interacting RNAs (piRNAs) are the most studied. However, new kinds of small ncRNAs are progressively being discovered, like tRNA-derived fragments, which have now been recognized to be the major RNA species in human cells. For a long time, small ncRNAs were considered as by-products from random degradation; nonetheless, there are increasing evidences that they are functional molecules with precise sequence structure, specific expression patterns and critical roles in gene regulation.\ud
Dysregulation of genes involved in cell proliferation, differentiation and/or apoptosis is associated with tumorigenic processes. Such as gene regulators, a wide variety of small ncRNAs have been demonstrated to be involved in tumor initiation and progression controlling and modulating cancer-related gene expression. Interestingly, besides cellular small ncRNAs, they have been also discovered in body fluids as stable circulating small ncRNAs carried within extracellular microvesicles (exosomes) or associated with Ago proteins. Numerous of them have been studied as promising non-invasive biomarkers for several kinds of diseases like cancer. Currently, breast cancer is the most common cancer and leading cause of cancer death among women worldwide. The HER2+ -breast cancer subtype has been described as one with the most aggressive phenotype. Albeit new therapies have been developed, more efforts to improve diagnosis, treatment and prognosis are needed.\ud
Here, we report the identification of two new circulating tRNA-derived fragments, 3’Glu-tRF-M and 5’Glu-tRF-M. Cloning experiments and in silico analyses suggest that they are processed by Dicer enzyme from mature Glutamic tRNA. We assessed their expression in different healthy and HER2+ -breast cancer samples from mice and humans by semi-quantitative PCR, Northern Blot and quantitative real-time PCR. Moreover cytoplasmatic location of both, 3’Glu-tRF-M and 5’Glu-tRF-M, was proved by an immunofluorescence assay. A significative decrease of 3’Glu-tRF-M expression was observed in both, mice and human individuals with HER2+ -breast cancer.\ud
We conclude hypothesizing that the neoplasia could regulate, directly or indirectly, 3’Glu-tRF-M expression, leading to its decrease. Since this variation seems to depend on tumor development status, outcome that will be confirmed in further studies, 3’Glu-tRF-M could be considered a future non-invasive biomarker for HER2+ -breast cancer
Characterization of Bacterial Translation Elongation Inhibitors
No full textResistance to antibiotics has increased and is still growing so that almost every human pathogen has acquired resistance to at least one class of antimicrobials in clinical use. As a result, every year bacterial pathogens infect more than 1/3 of the world population causing >2 million fatalities and hospital-acquired infections in Europe account for ca.175,000 deaths. In Italy ca. 7000 deaths are caused by bacterial infections acquired by about 6.7% of hospitalized patients. The fairly large number of fatalities caused by untreatable bacterial infections in Europe in recent years further underlies the existence of an antibiotic-emergency which renders even more formidable the health threat caused by infectious diseases by both traditional pathogens and\ud
emerging superbugs.\ud
In this contest, the need for new antibiotics has increased.\ud
The aim of my work is to study the mechanisms of action of two translational inhibitors called NAI003 and HygromycinA. NAI003, is a chemical derivative of the thiopeptide GE2270A an inhibitor of bacterial elongation factor Tu (EF-Tu), while HygromycinA is an old antibiotic (discovered in the 1953) whose mechanism of action and its location on the ribosome have not yet been elucidated at least at the molecular level
Apoliprotein A-IV as a new possible molecular “tool” to understand feline hepatic lipidosis physiopathology
No full textFeline Hepatic Lipidosis (FHL) represents one of the most common metabolic disorders in cats. Apolipoprotein (apo) A-IV is a protein known to participate in the regulation of various metabolic pathways, with special regards to lipid metabolism. The present study demonstrates a relation between hepatic lipid content and apo A-IV expression in rat and cat liver, opening a fascinating\ud
innovative hypothesis on FHL pathogenesis.\ud
Livers from cats (5) and rats (8) were processed to determine hepatic lipid content using Mojonnier method. Apo A-IV liver protein expression was assessed by ELISA using liver tissue extracts. Finally, samples of all livers were processed for histopathology and immunohistochemistry to confirm previously obtained results.\ud
Data show an interesting inverse proportion between hepatic lipid content and apo A-IV liver expression, highlighting differences between cat and rat lipid metabolism. Applying this comparative experimental approach, we suggest an innovative pathogenetic hypothesis which involves apo A-IV as a “new actor” molecule involved in FHL determinism and its potential role as a prodromal serological diagnostic marker
Peroxisome proliferator-activated receptor gamma (PPARγ): a new drug target to treat addiction and anxiety
No full textTopographic metrics in the Southern Sector of the Marche Foothills: possible implication of Rock Uplift and active Tectonics
No full textThe investigated area is situated in central Italy and it extends from the axial zone of the Umbria–Marche Apennines to the Adriatic Sea, including the southern sector of the Marche Region and belongs to the foredeep domain of the Apennines orogenic system, which has affected by tectonic activity up to very recent times.\ud
The rheology of outcropping deposits doesn’t allow the strain to be easily recorded at the outcrop scale. Thus, the quantitative geomorphic analysis can be provided a useful contribution to the study of recent tectonics. Some parameters, that quantify the channels morphology, as the Stream Length-Gradient (SL) Index [...] and the Steepness (Ks) Index [...], are generally used to detect anomalies on the expected concave-up equilibrium stream-profile, which can result in local abrupt changes in stream gradient (i.e., knickpoints) and/or broad convexities on stream long-profiles extending for tens of\ud
kilometres (i.e., knickzones).\ud
The main goal of this work is the study of the morphological and morphometrical features in the southern sector of the Marche Region, with the aim to gain new knowledge on the influences of rock resistance and rock uplift on the fluvial and topographic system.\ud
The analyses have been aimed at to test the sensitivity of both SL and Ks for evaluating active crustal deformations, acting at different wavelengths on land surface, within a low tectonically active thrust-and-fold belt. Additional purpose was the understanding of the\ud
pattern of regional differential crustal activity in the topographic arrangement of the study area.\ud
In this research project two sets of analysis were conducted. The first analysis was aimed at defining quantitatively the geometry of stream long-profiles along six adjacent trunk-valleys through different morphometric parameters. The objective of this first analysis was\ud
to identify and characterize the stream reaches and/or segments where the long-profiles exhibit anomalies on the typical concave up steady-state profile, respectively knickpoints and/or knickzones, possibly related to the activity of crustal deformation acting at different\ud
wavelengths. With the second analysis were investigated the general topographic features focusing on the spatial variation in the minimum, mean, and maximum elevations and in local relief values. To study topography at regional scale, were computed three swath profile, local relief map and topographic spatial filters at four different wavelengths.\ud
The results obtained from this work highlight, in the investigated area, four anomalies areas that are compatible with the sectors of the Periadriatic basin, split by transverse and oblique faults and on which a different tectonic and sedimentary evolution are present\ud
[...].\ud
Notably, the crustal differential uplift demonstrated to be the main process responsible for the formation of knickzones along the middle portions of the major rivers draining this sector of the Marche foothills. The quantitative dataset has shown useful for detecting\ud
large topographic features transversal to the trend of the main regional morphostructures, which revealed effective on controlling stream long-profiles and relief. Moreover, the combine method used in this work (stream channel metrics and topography analysis) provides an advantageous approach in an area characterized by lithologies that are unlikely to preserve o tectonic deformation, where the longitudinal profile channel analysis is not sufficient to identifies anomalies
Dynamics of a Trapped Particle in a Double-Well Potential
No full textPotential wells are widely studied entities nowadays, because of their wide range of applications in many fields of science. Experimental and technological improvements make it possible to design and control the potential shape. For instance, one can modify a single-well potential into\ud
a double well and backwards. To investigate this kind of problems, one needs to properly take into account the time-dependency of the system Hamiltonian.\ud
We used split operator method to study the dynamics of wavepacket in general, and in time-dependent potential wells in particular. While considering time-dependent potential wells, we concentrated on the case when a single-well is transformed into a double-well. Our goal was to explore the range of validity of the adiabatic theorem. We have made observations on the dynamics of the wavepacket for different barrier heights and widths. For each case, we estimated how long the switching time should be in order to leave the system in the ground state. In doing this, we established a link between the eigenvalues of potential well and the time taken by the wavepacket to be in the ground state of potential well. The greater the difference between the first two eigenvalues of the double well, the lesser the switching time requested to go from single- to double well.\ud
Moreover, we simulated the system dynamics while going from single- to asymmetric doublewell. We noticed that the superposition of left and right states is very fragile with respect to asymmetry. By introducing any asymmetry in the double-well, the wavepacket tends to be trapped in the deeper side of the potential well. While talking in terms of eigenvalues of asymmetric double-well, we again observed that the greater the difference between eigenvalues, the\ud
lesser the time needed by the wavepacket to be in ground state of double-well.\ud
Finally, we applied the theoretically discussed approach to estimate the switching time needed by a trapped ion to be in the ground state of a double-well potential, for realistic experimental parameters
Usos do direito subjetivo à liberdade religiosa.\ud Assistência religiosa na prisão.
No full textIs it possible that people in subaltern or minority positions use religious rights to favor themselves? This thesis orbits around this question.\ud
To ask this question, first it is necessary to check if the exercise of religious rights is really unequal, which is confirmed in the analysis of Brazilian experience of legal regulation of religion. Although such experience is different from more famous models of legal regulation of religion, it presents the same problems identified by the critical legal theory on religious freedom in other contexts. These problems integrate a vicious cycle: such inequality is invisible because the secular State may not deal with religion but, even though, it does regulate it, based on the understandings of the majority religion. By regulating religion, the State connects with religious groups, intervening in their organization and contributing to the transference of individual religious rights to religious organizations.\ud
The answer to this question requires a theoretical approach that does not paralyze before the problems identified by the critical legal theory on religious freedom. Among possible approaches, the cultural analysis of Law is appropriate because it recognizes the problems but also allows for the observation of other uses of the regulation of religion, by individuals and religious groups. Cultural analysis allows to see the lives of\ud
legal rules outside traditionally legal spaces such as courts and parliaments. Also, the relation between these rules and individuals does not resume to obedience or\ud
disobedience to Law, exercise or no exercise of legal rights. According to such approach, the uses of legal regulation and rights are more ample than these oppositional pairs. To better understand such uses, it is important to focus on the study of one religious right. This thesis, therefore, is also about the right to religious assistance in Brazilian prisons.\ud
Documentary research on the suppression of the official chaplaincy in Brazilian prisons, on the diverse Federate States regulations of religion and the ethnographic sketch of the production of the Resolution n. 8/2011 (Conselho Nacional de Política Criminal e Penitenciaria) show the mechanisms that maintain religious majorities understandings through secularism and also the interaction between legal regulation of religion –\ud
secularity, religious pluralism and freedom – and the priority of security in prisons. Literature review on comparative studies on religion in prison shows how extravagant can be the uses of the right to religious assistance. By the transference of the States’ obligation to recover inmates to religious organizations witch reinforces the transference of the individual right to religious assistance to religious organizations, the right to religious assistance can be used as a route to a deficient realization of others inmates’ rights such as material, social and legal assistance.\ud
The validity of such approach must be tested in other situations: in the study of legal regulation of religion in other places and in the study of such regulation through not religious rights. In this thesis, for not requiring a normative solution, it allowed to understand different concepts, actors and knowledge areas connected to the question