A questão do livre-arbítrio em John R. Searle: uma contraposição do naturalismo biológico ao fisicalismo e ao funcionalismo

This paper compares the theses of physicalism and functionalism – particularly the computacionalist line – with the biological naturalism of John Searle regarding the possibility of free will. In such contrast, each line is decomposed into its statements so that they can be reviewed. It is argued that the searlean biological naturalism can explain more than the other two philosophies on how free action can have the source of its motivation in what is external to the mental state that makes it beperformed. Finally, even if the issue of free will still is open, I shall argue that free will does not find any room in the scenario that the lines of physicalism and functionalism present

To methylate or not to methylate? Study of Mercury Speciation along\ud the Venetian Littoral System (Q-ALiVe project)

The biogeochemical cycle of mercury (Hg) is affected not only by the physical, chemical and hydrological characteristics of the environment, but also by changes in productivity and biodiversity. In waters the complexes of Hg are related to the salinity and to the load of dissolved organic carbon (DOC) in the dissolved and in the particulate phases. Surface and bottom seawater were sampled along the Venetian coast at ten sites with different characteristics. Samples were analyzed employing hyphenated techniques and LOD (limit of detection) and LOQ (limit of quantification) were quantified. Although for some samples both the species were under the LOQ, the presence of methyl mercury (CH3Hg+) and ionic mercury (Hg2+) at the same time in surface and in bottom waters were observed. Variability in CH3Hg+ concentrations may be due to changes in the phytoplankton communities, which in turn may be affected by nutrient loads from the catchment area and port mouths of the Venice Lagoon. Thus, monitoring these nutrient loads may be essential for the health of the Venetian littoral system, since they may affect blooms, methylation and hyper-bioaccumulation along the trophic web, with effects on the environment and on human health

Gene profiling of lung toxicity

Bleomycin is a potent anti-tumour compound used in the treatment of squamous cell carcinomas. An unfortunate side effect of this drug is pulmonary toxicity. The onset of this damage manifests as mild oedema and inflammation which eventually develops into pulmonary fibrosis. The ability to correctly identify patients showing early signs of lung injury could significantly reduce the morbidity associated with bleomycin treatment. As such, this study was undertaken to identify genetic markers of early oedema and inflammation. A model of mild pulmonary injury was induced by bleomycin. Conventional quantitative analysis of broncho-alveolar lavage was used to indicate the severity of the oedematous response, whilst morphological changes were identified by histology and electron microscopy. Macroarrays were used to measure the expression of multiple genes during mild, progressive and severe oedema. Following normalisation and statistical analysis, gene expression patterns were compared from saline- and bleomycin-treated rats. A variety of genes were differentially expressed during each model, with the number increasing with the severity of the oedema. A cluster and two individual genes were consistently expressed across two of the models of oedema. The magnitude of the changes in gene expression were quantified and confirmed by quantitative PCR. In summary, complete toxicological and histological characterisation of the bleomycin-induced model of pulmonary injury successfully identified specific endpoints of injury. This model proved to be ideal for studying differential gene expression in response to drug-induced pulmonary oedema. A cluster of ion channels and trafficking genes has the potential to act as a biomarker. Two specific genetic markers (Na+/CI- betaine/GABA transporter, glucocorticoid receptor), and a protein marker (cocoacrisp) have been identified for the oedema. In addition to these genes and protein being potential biomarkers of injury, they are also prospective targets for clinical treatment.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Phage display and experimental brain therapeutics

Phage display, a powerful polypeptide display technology, affords the rapid identification of peptides and proteins that interact with a target of interest The aims of the project were the phage display identification of peptides that interact with a druggable target in a brain disorder (glioblastoma multiforme) and the identification of peptides that serve as targeting vectors for brain delivery. Validation studies were undertaken to qualify the use of a cyclic 7-mer peptide phage library against targets including streptavidin and paracetamol chosen as examples of a large complex and small simple molecule, respectively. With the aim of identifying peptide phages that bind to the luminal surface of brain micro vasculature, a primary in-vitro porcine model of the blood-brain barrier (BBB) comprising primary brain capillary endothelial cells was established and characterised. An in-vivo phage display was undertaken in the rat with the aim of identifying peptide sequences that mediated translocation across the BBB into brain grey matter. A 7-mer cyclic peptide was identified with sequence AC-SYTSSTM-CGGGS that enhanced the uptake of phages into brain grey matter by 4-fold compared to control wild-type phages. This peptide may serve as a novel targeting vector for the delivery of a therapeutic cargo to the brain. Caveolin-1 was identified as a potential new therapeutic target in in-vitro models of grade IV astrocytomas (glioblastoma multiforme), with siRNA knockdown of caveolin-1 associated with reduced glioma cell proliferation and invasiveness. With the caveolin-1 scaffolding domain (aa 81-101 in the caveolin-1 protein) as a target, an in-vitro peptide phage selection was undertaken and identified a series of peptides that bind the scaffolding domain with high affinity. These peptides will serve as a template for the development of low molecular weight peptidomimetics that inhibit caveolin-1 function. In conclusion, the studies in this thesis have demonstrated the utility of phage display in experimental therapeutics of brain disorders.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

To methylate or not to methylate? Study of Mercury Speciation along the Venetian Littoral System (Q-ALiVe project)

The biogeochemical cycle of mercury (Hg) is affected not only by the physical, chemical and hydrological characteristics of the environment, but also by changes in productivity and biodiversity. In waters the complexes of Hg are related to the salinity and to the load of dissolved organic carbon (DOC) in the dissolved and in the particulate phases. Surface and bottom seawater were sampled along the Venetian coast at ten sites with different characteristics. Samples were analyzed employing hyphenated techniques and LOD (limit of detection) and LOQ (limit of quantification) were quantified. Although for some samples both the species were under the LOQ, the presence of methyl mercury (CH3Hg+) and ionic mercury (Hg2+) at the same time in surface and in bottom waters were observed. Variability in CH3Hg+ concentrations may be due to changes in the phytoplankton communities, which in turn may be affected by nutrient loads from the catchment area and port mouths of the Venice Lagoon. Thus, monitoring these nutrient loads may be essential for the health of the Venetian littoral system, since they may affect blooms, methylation and hyper-bioaccumulation along the trophic web, with effects on the environment and on human health

How does Low Back Pain Influence Muscle Activity during a Cyclical Dynamic Lifting Task?

Title How does LBP Influence Muscle Activity during a Cyclical Dynamic Lifting Task? Authors Andy Sanderson, Corrado Cescon, Nicola R. Heneghan, Alison Rushton, Marco Barbero, Pauline Kuithan, Deborah Falla Purpose Chronic non-specific low back pain (cLBP) is a leading cause of disability, limiting activity in 540 million people globally. High-density electromyography (HDEMG) has been used to investigate changes in back muscle activity in people with cLBP. Previous studies have utilised static or mono-planar tasks or focussed on small areas of the erector spinae (ES). This study uses innovative HDEMG and kinematic analysis to investigate the effect of cLBP on muscle activity and movement during a multi-planar lifting task. Methods Sixteen people with cLBP (8 male, age: 26.9±10.8 years) and sixteen age and gender-matched controls (7 male, age: 31.7±14.0 years) completed the study. HDEMG signals from the ES were detected with four 64-channel semi-disposable 13x5 electrode grids (2 grids bilaterally) covering the lumbar and thoraco-lumbar ES. Kinematic surface markers were placed over the back, enabling 3D motion capture. HDEMG and kinematic data were recorded continuously during a dynamic task involving the cyclical lifting of a 5kg box between 6 shelves for 10 cycles (~7 minutes). The shelves were arranged around the participant, at knee and sternal height, with one pair of shelves anterior and two pairs lateral. To the beat of a metronome, the participant moved the box between shelves, returning to a central shelf each time (10 movements). HDEMG amplitude data were normalised to the first cycle for each movement to a shelf, and factorial ANOVA’s used to compare subsequent cycles to the first. Results Kinematic analysis revealed no significant differences between groups in the movement pattern used to complete the lifting task (P>0.05 for all relevant outcomes). Despite similar movements, significant differences in muscle activity, were seen between groups. The cLBP group showed systematically higher amplitude, indicating higher levels of muscle activity, in 6/10 shelf movements (P0.05). Conclusion As the data were normalised and amplitude is a measure of muscle activity, these results indicate that for a majority of movements, the activity in the ES for the LBP group did not show as great a reduction over the task as that of the control group. These data therefore support an altered motor control strategy in participants with cLBP. While no differences were found in the movement strategy, likely due to the standardisation of the task, cLBP participants showed lower reductions in activity, indicating that already fatigued or dysfunctional muscles remained in use throughout the task

The SURF (Italian observational study for renal insufficiency evaluation in liver transplant recipients): A post-hoc between-sex analysis

Background: Female sex has been reported as an independent predictor of severe post-liver transplantation (LT) chronic kidney disease. We performed a by sex post-hoc analysis of the SURF study, that investigated the prevalence of renal impairment following LT, aimed at exploring possible differences between sexes in the prevalence and course of post-LT renal damage. Methods: All patients enrolled in the SURF study were considered evaluable for this sex-based analysis, whose primary objective was to evaluate by sex the proportion of patients with estimated Glomerular Filtration Rate (eGFR) < 60 ml/min/1.73m2 at inclusion and follow-up visit. Results: Seven hundred thirty-eight patients were included in our analysis, 76% males. The proportion of patients with eGFR < 60 mL/min/1.73 m2 was significantly higher in females at initial study visit (33.3 vs 22.8%; p = 0.005), but also before, at time of transplantation (22.9 vs 14.7%; p = 0.0159), as analyzed retrospectively. At follow-up, such proportion increased more in males than in females (33.9 vs 26.0%, p = 0.04). Mean eGFR values decreased over the study in both sexes, with no significant differences. Statistically significant M/F differences in patient distribution by O'Riordan eGFR levels were observed at time of transplant and study initial visit (p = 0.0005 and 0.0299 respectively), but not at follow-up. Conclusions: Though the limitation of being performed post-hoc, this analysis suggests potential sex differences in the prevalence of renal impairment before and after LT, encouraging further clinical research to explore such differences more in depth