Human biomonitoring: biomarkers, susceptibility, and nutrigenetics

The methods of molecular biology applied in epidemiological research lead us to the realm of molecular epidemiology, where there is immense potential for the establishment of associations between cancer and exposure to risk factors in lifestyle, profession, or pollution. Human biomonitoring consists, on the one hand, in research and identification of hazardous environmental conditions and, on the other hand, in the assessment of cancer risk following exposure to such conditions. Since carcinogenesis is a lengthy process, the biomarkers used to recognize biological abnormalities are selected and developed in the realm of molecular epidemiology. Such biomarkers are quantifiable and allow for the recognition of progression from normal to abnormal biological conditions at the molecular level. They can be categorized in biomarkers of exposure, effect, and genetic susceptibility. Genotoxicity biomarkers are a particular subset of effect biomarkers and are used to assess genomic instability caused by environmental or occupational exposure, being considered useful carcinogenesis predictors.

Fat intake interacts with polymorphisms of Caspase9, FasLigand and PPARgamma apoptotic genes in modulating Crohn's disease activity

Background & aims: Crohn’s disease (CD) is a multifactorial disease where resistance to apoptosis is one major defect. Also, dietary fat intake has been shown to modulate disease activity. We aimed to explore the interaction between four single nucleotide polymorphisms (SNPs) in apoptotic genes and dietary fat intake in modulating disease activity in CD patients. Methods: Polymerase Chain Reaction (PCR) and Restriction Fragment Length Polymorphism (RFLP) techniques were used to analyze Caspase9þ93C/T, FasLigand-843C/T, Peroxisome Proliferator-Activated Receptor gammaþ161C/T and Peroxisome Proliferator-Activated Receptor gamma Pro12Ala SNPs in 99 patients with CD and 116 healthy controls. Interactions between SNPs and fat intake in modulating disease activity were analyzed using regression analysis. Results: None of the polymorphisms analyzed influenced disease susceptibility and/or activity, but a high intake of total, saturated and monounsaturated fats and a higher ratio of n-6/n-3 polyunsaturated fatty acids (PUFA), was associated with a more active phenotype (p < 0.05). We observed that the detrimental effect of a high intake of total and trans fat was more marked in wild type carriers of the Caspase9þ93C/T polymorphism [O.R (95%CI) 4.64 (1.27e16.89) and O.R (95%CI) 4.84 (1.34e17.50)]. In the Peroxisome Proliferator-Activated Receptor gamma Pro12Ala SNP, we also observed that a high intake of saturated and monounsaturated fat was associated to a more active disease in wild type carriers [OR (95%CI) 4.21 (1.33e13.26) and 4.37 (1.52e12.51)]. Finally, a high intake of n-6 PUFA was associated with a more active disease in wild type carriers for the FasLigand-843C/T polymorphism [O.R (95%CI) 5.15 (1.07e24.74)]. Conclusions: To our knowledge, this is the first study to disclose a synergism between fat intake and SNPs in apoptotic genes in modulating disease activity in CD patients.

Assessment of genotoxicity of aflatoxin M1 and B1 contaminated milks after in vitro human digestion

Introduction - Milk is considered a complete food from the nutritional point of view. Milk can be exposed to various types of contamination, such as mycotoxins. These metabolites are naturally occurring toxic compounds produced by fungi. Several studies on milk samples have reported the presence of aflatoxin B1 (AFB1) and M1 (AFM1), due to the high incidence in samples intended for human consumption, carcinogenicity proven AFB1 and resistance of the contaminants to the process of digestion, making those available for intestinal absorption. Considering these aspects, the objective of this study was to evaluate the genotoxicity of milk samples contaminated by AFB1 and AFM1 before and after the action of lactic acid bacteria using Caco-2 intestinal human cells.

From unthinned continent to ocean: The deep structure of the West Iberia passive continental margin at 38 degrees N

The crustal and lithospheric mantle structure at the south segment of the west Iberian margin was investigated along a 370 km long seismic transect. The transect goes from unthinned continental crust onshore to oceanic crust, crossing the ocean-continent transition (OCT) zone. The wide-angle data set includes recordings from 6 OBSs and 2 inland seismic stations. Kinematic and dynamic modeling provided a 2D velocity model that proved to be consistent with the modeled free-air anomaly data. The interpretation of coincident multi-channel near-vertical and wide-angle reflection data sets allowed the identification of four main crustal domains: (i) continental (east of 9.4 degrees W); (ii) continental thinning (9.4 degrees W-9.7 degrees W): (iii) transitional (9.7 degrees W-similar to 10.5 degrees W); and (iv) oceanic (west of similar to 10.5 degrees W). In the continental domain the complete crustal section of slightly thinned continental crust is present. The upper (UCC, 5.1-6.0 km/s) and the lower continental crust (LCC, 6.9-7.2 km/s) are seismically reflective and have intermediate to low P-wave velocity gradients. The middle continental crust (MCC, 6.35-6.45 km/s) is generally unreflective with low velocity gradient. The main thinning of the continental crust occurs in the thinning domain by attenuation of the UCC and the LCC. Major thinning of the MCC starts to the west of the LCC pinchout point, where it rests directly upon the mantle. In the thinning domain the Moho slope is at least 13 degrees and the continental crust thickness decreases seaward from 22 to 11 km over a similar to 35 km distance, stretched by a factor of 1.5 to 3. In the oceanic domain a two-layer high-gradient igneous crust (5.3-6.0 km/s; 6.5-7.4 km/s) was modeled. The intra-crustal interface correlates with prominent mid-basement, 10-15 km long reflections in the multi-channel seismic profile. Strong secondary reflected PmP phases require a first order discontinuity at the Moho. The sedimentary cover can be as thick as 5 km and the igneous crustal thickness varies from 4 to 11 km in the west, where the profile reaches the Madeira-Tore Rise. In the transitional domain the crust has a complex structure that varies both horizontally and vertically. Beneath the continental slope it includes exhumed continental crust (6.15-6.45 km/s). Strong diffractions were modeled to originate at the lower interface of this layer. The western segment of this transitional domain is highly reflective at all levels, probably due to dykes and sills, according to the high apparent susceptibility and density modeled at this location. Sub-Moho mantle velocity is found to be 8.0 km/s, but velocities smaller than 8.0 km/s confined to short segments are not excluded by the data. Strong P-wave wide-angle reflections are modeled to originate at depth of 20 km within the lithospheric mantle, under the eastern segment of the oceanic domain, or even deeper at the transitional domain, suggesting a layered structure for the lithospheric mantle. Both interface depths and velocities of the continental section are in good agreement to the conjugate Newfoundland margin. A similar to 40 km wide OCT having a geophysical signature distinct from the OCT to the north favors a two pulse continental breakup.

Estudo da utilização de fibras em misturas betuminosas

A presente dissertação tem como objectivo principal aprofundar os conhecimentos sobre a incorporação de fibras em misturas betuminosas, em particular, sobre as misturas do tipo Stone Mastic Asphalt (SMA). Para este tipo de mistura betuminosa existe uma norma de produto europeia, a EN 13108-5:2006. Os ensaios tipo iniciais para efeitos de certificação CE das misturas estão contemplados na norma portuguesa NP EN 13108-20:2008, onde também são estipuladas as condições de ensaio. São descritos diversos tipos de fibras passíveis de serem utilizadas no fabrico da mistura betuminosa do tipo SMA, dando especial enfoque às misturas fabricadas com fibras celulósicas, uma vez que este tipo específico de mistura é frequentemente aplicado em camada de desgaste noutros países, com reconhecidas vantagens em termos de durabilidade e desempenho do pavimento. As misturas do tipo SMA são descritas, analisando-se métodos de formulação e métodos para a sua caracterização. Posteriormente, são apresentados e discutidos os trabalhos experimentais levados a cabo para um caso concreto. Os ensaios realizados permitiram caracterizar a mistura quanto à sensibilidade à água, ao seu módulo de rigidez e resistência à deformação permanente. Conclui-se que a mistura do tipo SMA com a incorporação de fibras analisada, apresenta bom comportamento à deformação permanente e boa resistência á acção da água, comparativamente às misturas betuminosas tradicionais aplicadas em camada de desgaste.

Especulação em mercado bolsista : análise técnica : o caso Nasdaq-100 perante a crise subprime

Mestrado em Controlo de Gestão e dos Negócios