Pacta sunt servanda versus the social role of contracts: the case of Brazilian agriculture contracts

This study explores the instability created by contradictory court decisions related with contract breaches. Forward marketing contracts represent an important source of resources to finance Brazilian agriculture, however a large number of contract breaches were observed during a period of marked increase in soy prices. The study analyzed 161 judicial appeal decisions and a survey was carried with 70 farmers. The results show the difference of judges' interpretation and the existence of second order effects. The effects of court decisions were more requirements of guarantees and the reduction in the number of contracts. Those soybean farmers who did not breach their contracts have also been negatively affected by the strategic reactions of trading and processing companies. The concept of "social function of the contract" introduced in Brazilian civil code led to a higher degree of instability in contracts, raising transaction costs and motivating private economic sanctions.

Role of the amygdala in the reinforcement omission effect

The reinforcement omission effect (ROE) has been attributed to both motivational and attentional consequences of surprising reinforcement omission. Recent evidence suggests that the basolateral complex of the amygdala is involved in motivational components related to reinforcement value, whereas the central nucleus of the amygdala is involved in the processing of the attentional consequences of surprise. This study was designed to verify whether the mechanisms involved in the ROE depend on the integrity of either the basolateral amygdala complex or central nucleus of the amygdala. The ROE was evaluated in rats with lesions of either the central nucleus or basolateral complex of the amygdala and trained on a fixed-interval schedule procedure (Experiment 1) and fixed-interval with limited hold signaled schedule procedure (Experiment 2). The results of Experiment 1 showed that sham-operated rats and rats with lesions of either the central nucleus or basolateral area displayed the ROE. In contrast, in Experiment 2, subjects with lesions of the central nucleus or basolateral complex of the amygdala exhibited a smaller ROE compared with sham-operated subjects. Thus, the effects of selective lesions of amygdala subregions on the ROE in rats depended on the training procedure. Furthermore, the absence of differences between the lesioned groups in either experiment did not allow the dissociation of attentional or motivational components of the ROE with functions of specific areas of the amygdala. Thus, results did not show a functional double-dissociation between the central nucleus and basolateral area in the ROE.

Coastline changes and sedimentation related with the opening of an artificial channel: The Valo Grande Delta, SE Brazil

The role played by human activity in coastline changes indicates a general tendency of retreating coasts, especially deltaic environments, as a result of the recent trend of sea level rise as well as the blockage of the transfer of sediments towards the coast, especially due to the construction of dams. This is particularly important in deltaic environments which are suffering a dramatic loss of area in the last decades. In contrast, in this paper, we report the origin and evolution of an anthropogenic delta, the Valo Grande delta, on the south-eastern Brazilian coast, whose origin is related to the opening of an artificial channel and the diversion of the main flow of the Ribeira de Iguape River. The methodology included the analysis of coastline changes, bathymetry and coring, which was used to determine the sedimentation rates and grain-size changes over time. The results allowed us to recognize the different facies of the anthropogenic delta and to establish its lateral and vertical depositional trends. Despite not being very frequent, anthropogenic deltas represent a favorable environment for the record of natural and anthropogenic changes in historical times and, thus, deserve more attention from researchers of different subjects

Laser therapy and pain-related behavior after injury of the inferior alveolar nerve: possible involvement of neurotrophins

Nerve-related complications have been frequently reported in dental procedures, and a very frequent type of occurrence involves the inferior alveolar nerve (IAN). The nerve injury in humans often results in persistent pain accompanied by allodynia and hyperalgesia. In this investigation, we used an experimental IAN injury in rats, which was induced by a Crile hemostatic clamp, to evaluate the effects of laser therapy on nerve repair. We also studied the nociceptive behavior (von Frey hair test) before and after the injury and the behavioral effects of treatment with laser therapy (emitting a wavelength of 904 nm, output power of 70 Wpk, a spot area of *0.1 cm2, frequency of 9500 Hz, pulse time 60 ns and an energy density of 6 J/cm2). As neurotrophins are essential for the process of nerve regeneration, we used immunoblotting techniques to preliminarily examine the effects of laser therapy on the expression of nerve growth factor (NGF) and brainderived neurotrophic factor (BDNF). The injured animals treated with laser exhibited an improved nociceptive behavior. In irradiated animals, there was an enhanced expression of NGF (53%) and a decreased BDNF expression (40%) after laser therapy. These results indicate that BDNF plays a locally crucial role in pain-related behavior development after IAN injury, increasing after lesions (in parallel to the installation of pain behavior) and decreasing with laser therapy (in parallel to the improvement of pain behavior). On the other hand, NGF probably contributes to the repair of nerve tissue, in addition to improving the pain-related behavior.

Acellular and "low" pertussis vaccines: adverse events and the role of mutations

Objective: to discuss the current PAHO recommendation that does not support the substitution of traditional cellular DTP vaccine by acellular DTP, and the role of mutations, in humans, as the main cause of rare adverse events, such as epileptic-like convulsions, triggered by pertussis vaccine. Data review: the main components related to toxic effects of cellular pertussis vaccines are the lipopolysaccharide of bacterial cell wall and pertussis toxin. The removal of part of lipopolysaccharide layer has allowed the creation of a safer cellular pertussis vaccine, with costs comparable to the traditional cellular vaccine, and which may be a substitute for the acellular vaccine. Conclusion: The new methodology introduced by Instituto Butantan allows for the development of a new safer pertussis vaccine with low LPS content (Plow), and the use of the lipopolysaccharide obtained in the process in the production of monophosphoryl lipid A. This component has shown potent adjuvant effect when administered together with influenza inactivated vaccine, making possible to reduce the antigen dose, enhancing the production capacity and lowering costs.

Women's subjective and objective health over time : the role of psychosocial conditions and physiological stress responses

Today, health problems are likely to have a complex and multifactorial etiology, whereby psychosocial factors interact with behaviour and bodily responses. Women generally report more health problems than men. The present thesis concerns the development of women’s health from a subjective and objective perspective, as related to psychosocial living conditions and physiological stress responses. Both cross-sectional and longitudinal studies were carried out on a representative sample of women. Data analysis was based on a holistic person-oriented approach as well as a variable approach. In Study I, the women’s self-reported symptoms and diseases as well as self-rated general health status were compared to physician-rated health problems and ratings of the general health of the women, based on medical examinations. The findings showed that physicians rated twice as many women as having poor health compared to the ratings of the women themselves. Moreover, the symptom ”a sense of powerlessness” had the highest predictive power for self-rated general health. Study II investigated individual and structural stability in symptom profiles between adolescence and middle-age as related to pubertal timing. There was individual stability in symptom reporting for nearly thirty years, although the effect of pubertal timing on symptom reporting did not extend into middle-age. Study III explored the longitudinal and current influence of socioeconomic and psychosocial factors on women’s self-reported health. Contemporary factors such as job strain, low income, financial worries, and double exposure in terms of high job strain and heavy domestic responsibilities increased the risk for poor self-reported health in middle-aged women. In Study IV, the association between self-reported symptoms and physiological stress responses was investigated. Results revealed that higher levels of medically unexplained symptoms were related to higher levels of cortisol, cholesterol, and heart rate. The empirical findings are discussed in relation to existing models of stress and health, such as the demand-control model, the allostatic load model, the biopsychosocial model, and the multiple role hypothesis. It was concluded that women’s health problems could be reduced if their overall life circumstances were improved. The practical implications of this might include a redesign of the labour market giving women more influence and control over their lives, both at and away from work.

Role of caloric content on gastric emptying in humans

[EN] 1. This study examined the effects of caloric content (caloric density and the nature of calories) on the rate of gastric emptying using the double-sampling gastric aspiration technique. Four test meals of 600 ml (glucose, 0.1 kcal ml-1; pea and whey peptide hydrolysates, both 0.2 kcal ml-1; milk protein, 0.7 kcal ml-1) were tested in six healthy subjects in random order on four separate occasions. 2. The glucose solution was emptied the fastest with a half-time of 9.4 +/- 1.2 min (P < 0.05) and the milk protein the slowest with a half-time of 26.4 +/- 10.0 min (P < 0.05); the pea peptide hydrolysate and whey peptide hydrolysate solutions had half-times of emptying of 16.3 +/- 5.4 and 17.2 +/- 6.1 min, respectively. The rates of gastric emptying for the peptide hydrolysate solutions derived from different protein sources were not different. 3. Despite the lower rate of gastric emptying for the milk protein solution, the rate of caloric delivery to the duodenum during the early phase of the gastric emptying process was higher than that for the other three solutions (46.3 +/- 6, 63.5 +/- 22, 62.5 +/- 19 and 113.8 +/- 25 cal min-1 kg-1 for the glucose, pea peptide hydrolysate, whey peptide hydrolysate and milk protein meals, respectively; P < 0.05). The caloric density of the test solutions was linearly related to the half-time of gastric emptying (r = 0.96, P < 0.05) as well as to the rate at which calories were delivered to the duodenum (r = 0.99, P < 0.001). 4. This study demonstrates that the rate of gastric emptying is a function of the caloric density of the ingested meal and that a linear relationship exists between these variables. Furthermore, the nature of the calories seems to play a minor role in determining the rate of gastric emptying in humans.

Role of reactive oxygen and nitrogen species in the response of Prunus spp. to bicarbonate

In calcareous soils, which are a large share of agricultural soils worldwide, iron availability is limited. Consequently, the whole plant physiology is affected, because of the key role of iron in redox metabolism, resulting in reduced crop yield and quality. Peach cultivation is economically important in northern Italy, and is easily subjected to iron chlorosis. The management of iron nutrition in peach includes grafting on bicarbonate-tolerant rootstocks; other forms of management may be expensive and environmentally impacting. Four genotypes, used as rootstocks for peach and characterized by different degrees of tolerance to chlorosis, were tested in vitro on optimal and bicarbonate-enriched medium. Their redox status and antioxidant responses were assayed; the production and possible roles of nitric oxide (NO) and related compounds were also studied. The most sensitive genotypes show a stronger reduction of the antioxidant enzymatic activities and an increased oxidative stress. A high production of NO was found to be associated to resistant genotypes, whereas sensitive genotypes reacted to stress by downregulating nitrosoglutathione reductase activity. Therefore, NO is proposed to improve the internal iron availability, or to stimulate iron intake.

Investigating the role of single point mutations in the human proteome: a computational study

In the post genomic era with the massive production of biological data the understanding of factors affecting protein stability is one of the most important and challenging tasks for highlighting the role of mutations in relation to human maladies. The problem is at the basis of what is referred to as molecular medicine with the underlying idea that pathologies can be detailed at a molecular level. To this purpose scientific efforts focus on characterising mutations that hamper protein functions and by these affect biological processes at the basis of cell physiology. New techniques have been developed with the aim of detailing single nucleotide polymorphisms (SNPs) at large in all the human chromosomes and by this information in specific databases are exponentially increasing. Eventually mutations that can be found at the DNA level, when occurring in transcribed regions may then lead to mutated proteins and this can be a serious medical problem, largely affecting the phenotype. Bioinformatics tools are urgently needed to cope with the flood of genomic data stored in database and in order to analyse the role of SNPs at the protein level. In principle several experimental and theoretical observations are suggesting that protein stability in the solvent-protein space is responsible of the correct protein functioning. Then mutations that are found disease related during DNA analysis are often assumed to perturb protein stability as well. However so far no extensive analysis at the proteome level has investigated whether this is the case. Also computationally methods have been developed to infer whether a mutation is disease related and independently whether it affects protein stability. Therefore whether the perturbation of protein stability is related to what it is routinely referred to as a disease is still a big question mark. In this work we have tried for the first time to explore the relation among mutations at the protein level and their relevance to diseases with a large-scale computational study of the data from different databases. To this aim in the first part of the thesis for each mutation type we have derived two probabilistic indices (for 141 out of 150 possible SNPs): the perturbing index (Pp), which indicates the probability that a given mutation effects protein stability considering all the “in vitro” thermodynamic data available and the disease index (Pd), which indicates the probability of a mutation to be disease related, given all the mutations that have been clinically associated so far. We find with a robust statistics that the two indexes correlate with the exception of all the mutations that are somatic cancer related. By this each mutation of the 150 can be coded by two values that allow a direct comparison with data base information. Furthermore we also implement computational methods that starting from the protein structure is suited to predict the effect of a mutation on protein stability and find that overpasses a set of other predictors performing the same task. The predictor is based on support vector machines and takes as input protein tertiary structures. We show that the predicted data well correlate with the data from the databases. All our efforts therefore add to the SNP annotation process and more importantly found the relationship among protein stability perturbation and the human variome leading to the diseasome.

Sleep-related changes in blood pressure in hypocretin-deficient narcoleptic mice

Objectives. Blood pressure (BP) physiologically has higher and lower values during the active and rest period, respectively. Subjects failing to show the appropriate BP decrease (10-20%) on passing form diurnal activity to nocturnal rest and sleep have increased risk of target organ damage at the cardiac, vascular and cerebrovascular levels. Hypocretin (HCRT) releasing neurons, mainly located in the lateral hypothalamus, project widely to the central nervous system. Thus HCRT neurons are involved in several autonomic functions, including BP regulation. HCRT neurons also play a key role in wake-sleep cycle regulation, the lack of which becomes evident in HCRT-deficient narcoleptic patients. I investigated whether chronic lack of HCRT signaling alters BP during sleep in mouse models of narcolepsy. Methods. The main study was performed on HCRT-ataxin3 transgenic mice (TG) with selective post-natal ablation of HCRT neurons, HCRT gene knockout mice (KO) with preserved HCRT neurons, and Wild-Type control mice (WT) with identical genetic background. Experiments where replicated on TG and WT mice with hybrid genetic background (hTG and hWT, respectively). Mice were implanted with a telemetric pressure transducer (TA11PA-C10, DSI) and electrodes for discriminating wakefulness (W), rapid-eye-movement sleep (REMS) and non-REMS (NREMS). Signals were recorded for 3 days. Mean BP values were computed in each wake-sleep state and analyzed by ANOVA and t-test with significance at p<0.05. Results. The decrease in BP between either NREMS or REMS and W was significantly blunted in TG and KO with respect to WT as well as in hTG with respect to hWT. Conclusions. Independently from the genetic background, chronic HCRT deficiency leads to a decreased BP difference between W and sleep potentially adverse in narcoleptic subjects. These data suggest that HCRT play an important role in the sleep-dependent cardiovascular control.

Depicting the role of CDKN2A/ARF alterations in adult BCR-ABL1-positive acute lymphoblastic leukemia patients: from genomic deletions to prognostic impact

This 9p21 locus, encode for important proteins involved in cell cycle regulation and apoptosis containing the p16/CDKN2A (cyclin-dependent kinase inhibitor 2a) tumor suppressor gene and two other related genes, p14/ARF and p15/CDKN2B. This locus, is a major target of inactivation in the pathogenesis of a number of human tumors, both solid and haematologic, and is a frequent site of loss or deletion also in acute lymphoblastic leukemia (ALL) ranging from 18% to 45% 1. In order to explore, at high resolution, the frequency and size of alterations affecting this locus in adult BCR-ABL1-positive ALL and to investigate their prognostic value, 112 patients (101 de novo and 11 relapse cases) were analyzed by genome-wide single nucleotide polymorphisms arrays and gene candidate deep exon sequencing. Paired diagnosis-relapse samples were further available and analyzed for 19 (19%) cases. CDKN2A/ARF and CDKN2B genomic alterations were identified in 29% and 25% of newly diagnosed patients, respectively. Deletions were monoallelic in 72% of cases and in 43% the minimal overlapping region of the lost area spanned only the CDKN2A/2B gene locus. The analysis at the time of relapse showed an almost significant increase in the detection rate of CDKN2A/ARF loss (47%) compared to diagnosis (p = 0.06). Point mutations within the 9p21 locus were found at very low level with only a non-synonymous substition in the exon 2 of CDKN2A. Finally, correlation with clinical outcome showed that deletions of CDKN2A/B are significantly associated with poor outcome in terms of overall survival (p = 0.0206), disease free-survival (p = 0.0010) and cumulative incidence of relapse (p = 0.0014). The inactivation of 9p21 locus by genomic deletions is a frequent event in BCR-ABL1-positive ALL. Deletions are frequently acquired at the leukemia progression and work as a poor prognostic marker.

Determinants of child undernutrition in India. A micro-case study to operationalize the Capability Approach

The present research aims at shedding light on the demanding puzzle characterizing the issue of child undernutrition in India. Indeed, the so called ‘Indian development paradox’ identifies the phenomenon according to which higher level of income per capita is recorded alongside a lethargic reduction in the proportion of underweight children aged below three years. Thus, in the time period occurring from 2000 to 2005, real Gross Domestic Production per capita has annually grown at 5.4%, whereas the proportion of children who are underweight has declined from 47% to 46%, a mere one point percent. Such trend opens up the space for discussing the traditionally assumed linkage between income-poverty and undernutrition as well as food intervention as the main focus of policies designed to fight child hunger. Also, it unlocks doors for evaluating the role of an alternative economic approach aiming at explaining undernutrition, such as the Capability Approach. The Capability Approach argues for widening the informational basis to account not only for resources, but also for variables related to liberties, opportunities and autonomy in pursuing what individuals value.The econometric analysis highlights the relevance of including behavioral factors when explaining child undernutrition. In particular, the ability of the mother to move freely in the community without the need of asking permission to her husband or mother-in-law is statistically significant when included in the model, which accounts also for confounding traditional variables, such as economic wealth and food security. Also, focusing on agency, results indicates the necessity of measuring autonomy in different domains and the need of improving the measurement scale for agency data, especially with regards the domain of household duties. Finally, future research is required to investigate policy venues for increasing agency in women and in the communities they live in as viable strategy for reducing the plague of child undernutrition in India.

Urban food planning, city logistics and sustainability: the role of the wholesale produce market. The cases of Parma and Bologna food hubs.

At global level, the population is increasingly concentrating in the cities. In Europe, around 75% of the population lives in urban areas and, according to the European Environmental Agency (2010), urban population is foreseen to increase up to 80 % by 2020. At the same time, the quality of life in the cities is declining and urban pollution keeps increasing in terms of carbon dioxide (CO2) emissions, waste, noise, and lack of greenery. Many of European cities struggle to cope with social, economic and environmental problems resulting from pressures such as overcrowding or decline, social inequity, health problems related to food security and pollution. Nowadays local authorities try to solve these problems related to the environmental sustainability through various urban logistics measures, which directly and indirectly affect the urban food supply system, thus an integrated approach including freight transport and food provisioning policies issues is needed. This research centres on the urban food transport system and its impact on the city environmental sustainability. The main question that drives the research analysis is "How the urban food distribution system affects the ecological sustainability in modern cities?" The research analyses the city logistics project for food transport implemented in Parma, Italy, by the wholesale produce market. The case study investigates the renewed role of the wholesale market in the urban food supply chain as commercial and logistic operator, referring to the concept of food hub. Then, a preliminary analysis on the urban food transport for the city of Bologna is presented. The research aims at suggesting a methodological framework to estimate the urban food demand, the urban food supply and to assess the urban food transport performance, in order to identify external costs indicators that help policymakers in evaluating the environmental sustainability of different logistics measures

Atomic Force Microscopy Studies of the Amyloidogenic Processes of Intrinsically Unstructured Proteins related to Neurodegenerative Diseases

Protein aggregation and formation of insoluble aggregates in central nervous system is the main cause of neurodegenerative disease. Parkinson’s disease is associated with the appearance of spherical masses of aggregated proteins inside nerve cells called Lewy bodies. α-Synuclein is the main component of Lewy bodies. In addition to α-synuclein, there are more than a hundred of other proteins co-localized in Lewy bodies: 14-3-3η protein is one of them. In order to increase our understanding on the aggregation mechanism of α-synuclein and to study the effect of 14-3-3η on it, I addressed the following questions. (i) How α-synuclein monomers pack each other during aggregation? (ii) Which is the role of 14-3-3η on α-synuclein packing during its aggregation? (iii) Which is the role of 14-3-3η on an aggregation of α-synuclein “seeded” by fragments of its fibrils? In order to answer these questions, I used different biophysical techniques (e.g., Atomic force microscope (AFM), Nuclear magnetic resonance (NMR), Surface plasmon resonance (SPR) and Fluorescence spectroscopy (FS)).

Bifidobacterium - Human Host Interaction: Role of Human Plasminogen

Bifidobacterium is an important genus of the human gastrointestinal microbiota, affecting several host physiological features. Despite the numerous Bifidobacterium related health-promoting activities, there is still a dearth of information about the molecular mechanisms at the basis of the interaction between this microorganism and the host. Bacterial surface associated proteins may play an important role in this interaction because of their ability to intervene with host molecules, as recently reported for the host protein plasminogen. Plasminogen is the zymogen of the trypsin-like serine protease plasmin, an enzyme with a broad substrate specificity. Aim of this thesis is to deepen the knowledge about the interaction between Bifidobacterium and the human plasminogen system and its role in the Bifidobacterium-host interaction process. As a bifidobacterial model, B. animalis subsp. lactis BI07 has been used because of its large usage in dairy and pharmaceutical preparations. We started from the molecular characterization of the interaction between plasminogen and one bifidobacterial plasminogen receptor, DnaK, a cell wall protein showing high affinity for plasminogen, and went on with the study of the impact of intestinal environmental factors, such as bile salts and inflammation, on the plasminogen-mediated Bifidobacterium-host interaction. According to our in vitro findings, by enhancing the activation of the bifidobacterial bound plasminogen to plasmin, the host inflammatory response results in the decrease of the bifidobacterial adhesion to the host enterocytes, favouring bacterial migration to the luminal compartment. Conversely, in the absence of inflammation, plasminogen acts as a molecular bridge between host enterocytes and bifidobacteria, enhancing Bifidobacterium adhesion. Furthermore, adaptation to physiological concentrations of bile salts enhances the capability of this microorganism to interact with the host plasminogen system. The host plasminogen system thus represents an important and flexible tool used by bifidobacteria in the cross-talk with the host.