Modern cancer epidemiological research: genetic polymorphisms and environment

Individual cancer susceptibility seems to be related to factors such as changes in oncogenes and tumor suppressor genes expression, and differences in the action of metabolic enzymes and DNA repair regulated by specific genes. Epidemiological studies on genetic polymorphisms of human xenobiotics metabolizing enzymes and cancer have revealed low relative risks. Research considering genetic polymorphisms prevalence jointly with environmental exposures could be relevant for a better understanding of cancer etiology and the mechanisms of carcinogenesis and also for new insights on cancer prognosis. This study reviews the approaches of molecular epidemiology in cancer research, stressing case-control and cohort designs involving genetic polymorphisms, and factors that could introduce bias and confounding in these studies. Similarly to classical epidemiological research, genetic polymorphisms requires considering aspects of precision and accuracy in the study design.

The influence of genetic polymorphisms in XRCC3 and ADH5 genes on the frequency of genotoxicity biomarkers in workers exposed to formaldehyde

The International Agency for Research on Cancer classified formaldehyde as carcinogenic to humans because there is “sufficient epidemiological evidence that it causes nasopharyngeal cancer in humans”. Genes involved in DNA repair and maintenance of genome integrity are critically involved in protecting against mutations that lead to cancer and/or inherited genetic disease. Association studies have recently provided evidence for a link between DNA repair polymorphisms and micronucleus (MN) induction. We used the cytokinesis-block micronucleus (CBMN assay) in peripheral lymphocytes and MN test in buccal cells to investigate the effects of XRCC3 Thr241Met, ADH5 Val309Ile, and Asp353Glu polymorphisms on the frequency of genotoxicity biomarkers in individuals occupationally exposed to formaldehyde (n = 54) and unexposed workers (n = 82). XRCC3 participates in DNA double-strand break/recombination repair, while ADH5 is an important component of cellular metabolism for the elimination of formaldehyde. Exposed workers had significantly higher frequencies (P < 0.01) than controls for all genotoxicity biomarkers evaluated in this study. Moreover, there were significant associations between XRCC3 genotypes and nuclear buds, namely XRCC3 Met/Met (OR = 3.975, CI 1.053–14.998, P = 0.042) and XRCC3 Thr/Met (OR = 5.632, CI 1.673–18.961, P = 0.005) in comparison with XRCC3 Thr/Thr. ADH5 polymorphisms did not show significant effects. This study highlights the importance of integrating genotoxicity biomarkers and genetic polymorphisms in human biomonitoring studies.

Corporate brand identity management in a technological faculty – how brand relationships influence students and companies reputations

Identity is traditionally defined as an emission concept [1]. Yet, some research points out that there are external factors that can influence it [2]; [3]; [4]. This subject is even more relevant if one considers corporate brands. According to Aaker [5] the number, the power and the credibility of corporate associations are bigger in the case of corporate brands. Literature recognizes the influence of relationships between companies in identity management. Yet, given the increasingly important role of corporate brands, it is surprising that to date no attempt to evaluate that influence has been made in the management of corporate brand identity. Also Keller and Lehman [6] highlight relationships and costumer experience as two areas requiring more investigation. In line with this, the authors intend to develop an empirical research in order to evaluate the influence of relationships between brands in the identity of corporate brand from an internal perspective by interviewing internal stakeholders (brand managers and internal clients). This paper is organized by main contents: theoretical background, research methodology, data analysis and conclusions and finally cues to future investigation.

Genetic population structure and connectivity of Azorean limpets

Ocean Science Meeting. Hawaii Convention Center, Honolulu, Hawaii, USA, 23-28 de Fevereiro.

Solution enthalpies of 1,4-dioxane: Study of solvent effects through quantitative structure-property relationships

Solution enthalpies of 1,4-dioxane have been obtained in 15 protic and aprotic solvents at 298.15 K. Breaking the overall process through the use of Solomonov's methodology the cavity term was calculated and interaction enthalpies (Delta H-int) were determined. Main factors involved in the interaction enthalpy have been identified and quantified using a QSPR approach based on the TAKA model equation. The relevant descriptors were found to be pi* and beta, which showed, respectively, exothermic and endothermic contributions. The magnitude of pi* coefficient points toward non-specific solute-solvent interactions playing a major role in the solution process. The positive value of the beta coefficient reflects the endothermic character of the solvents' hydrogen bond acceptor (HBA) basicity contribution, indicating that solvent molecules engaged in hydrogen bonding preferentially interact with each other rather than with 1,4-dioxane. (C) 2013 Elsevier B.V. All rights reserved.

Estudo morfológico e filogenético das subespécies Daucus carota ssp. Azoricus e Daucus carota ssp. Maritimus na ilha de S. Miguel

Dissertação de Mestrado, Biodiversidade e Biotecnologia Vegetal, 17 de Março de 2015, Universidade dos Açores.

Clinical and genetic factors predicting response to therapy in patients with Crohn’s disease

Aim - To identify clinical and/or genetic predictors of response to several therapies in Crohn’s disease (CD) patients. Methods - We included 242 patients with CD (133 females) aged (mean ± standard deviation) 39 ± 12 years and a disease duration of 12 ± 8 years. The single-nucleotide polymorphisms (SNPs) studied were ABCB1 C3435T and G2677T/A, IL23R G1142A, C2370A, and G9T, CASP9 C93T, Fas G670A and LgC844T, and ATG16L1 A898G. Genotyping was performed with real-time PCR with Taqman probes. Results - Older patients responded better to 5-aminosalicylic acid (5-ASA) and to azathioprine (OR 1.07, p = 0.003 and OR 1.03, p = 0.01, respectively) while younger ones responded better to biologicals (OR 0.95, p = 0.06). Previous surgery negatively influenced response to 5-ASA compounds (OR 0.25, p = 0.05), but favoured response to azathioprine (OR 2.1, p = 0.04). In respect to genetic predictors, we observed that heterozygotes for ATGL16L1 SNP had a significantly higher chance of responding to corticosteroids (OR 2.51, p = 0.04), while homozygotes for Casp9 C93T SNP had a lower chance of responding both to corticosteroids and to azathioprine (OR 0.23, p = 0.03 and OR 0.08, p = 0.02,). TT carriers of ABCB1 C3435T SNP had a higher chance of responding to azathioprine (OR 2.38, p = 0.01), while carriers of ABCB1 G2677T/A SNP, as well as responding better to azathioprine (OR 1.89, p = 0.07), had a lower chance of responding to biologicals (OR 0.31, p = 0.07), which became significant after adjusting for gender (OR 0.75, p = 0.005). Conclusions - In the present study, we were able to identify a number of clinical and genetic predictors of response to several therapies which may become of potential utility in clinical practice. These are preliminary results that need to be replicated in future pharmacogenomic studies.

Common genetic polymorphisms in the ABCB1 gene are associated with risk of major depressive disorder in male Portuguese individuals

Major depressive disorder (MDD) is a highly prevalent disorder, which has been associated with an abnormal response of the hypothalamus–pituitary–adrenal (HPA) axis. Reports have argued that an abnormal HPA axis response can be due to an altered P-Glycoprotein (P-GP) function. This argument suggests that genetic polymorphisms in ABCB1 may have an effect on the HPA axis activity; however, it is still not clear if this influences the risk of MDD. Our study aims to evaluate the effect of ABCB1 C1236T, G2677TA and C3435T genetic polymorphisms on MDD risk in a subset of Portuguese patients. DNA samples from 80 MDD patients and 160 control subjects were genotyped using TaqMan SNP Genotyping assays. A significant protection for MDD males carrying the T allele was observed (C1236T: odds ratio (OR) = 0.360, 95% confidence interval [CI]: [0.140– 0.950], p = 0.022; C3435T: OR= 0.306, 95% CI: [0.096–0.980], p = 0.042; and G2677TA: OR= 0.300, 95% CI: [0.100– 0.870], p = 0.013). Male Portuguese individuals carrying the 1236T/2677T/3435T haplotype had nearly 70% less risk of developing MDD (OR = 0.313, 95% CI: [0.118–0.832], p = 0.016, FDR p = 0.032). No significant differences were observed regarding the overall subjects. Our results suggest that genetic variability of the ABCB1 is associated with MDD development in male Portuguese patients. To the best of our knowledge, this is the first report in Caucasian samples to analyze the effect of these ABCB1 genetic polymorphisms on MDD risk.

Fractional dynamics of genetic algorithms using hexagonal space tessellation

The paper formulates a genetic algorithm that evolves two types of objects in a plane. The fitness function promotes a relationship between the objects that is optimal when some kind of interface between them occurs. Furthermore, the algorithm adopts an hexagonal tessellation of the two-dimensional space for promoting an efficient method of the neighbour modelling. The genetic algorithm produces special patterns with resemblances to those revealed in percolation phenomena or in the symbiosis found in lichens. Besides the analysis of the spacial layout, a modelling of the time evolution is performed by adopting a distance measure and the modelling in the Fourier domain in the perspective of fractional calculus. The results reveal a consistent, and easy to interpret, set of model parameters for distinct operating conditions.

Antioxidant properties of hydroxycinnamic acids: a review of structure- activity relationships

Hydroxycinnamic acids (HCAs) are important phytochemicals possessing significant biological properties. Several investigators have studied in vitro antioxidant activity of HCAs in detail. In this review, we have gathered the studies focused on the structure-activity relationships (SARs) of these compounds that have used medicinal chemistry to generate more potent antioxidant molecules. Most of the reports indicated that the presence of an unsaturated bond on the side chain of HCAs is vital to their activity. The structural features that were reported to be of importance to the antioxidant activity were categorized as follows: modifications of the aromatic ring, which include alterations in the number and position of hydroxy groups and insertion of electron donating or withdrawing moieties as well as modifications of the carboxylic function that include esterification and amidation process. Furthermore, reports that have addressed the influence of physicochemical properties including redox potential, lipid solubility and dissociation constant on the antioxidant activity were also summarized. Finally, the pro-oxidant effect of HCAs in some test systems was addressed. Most of the investigations concluded that the presence of ortho-dihydroxy phenyl group (catechol moiety) is of significant importance to the antioxidant activity, while, the presence of three hydroxy groups does not necessarily improve the activity. Optimization of the structure of molecular leads is an important task of modern medicinal chemistry and its accomplishment relies on the careful assessment of SARs. SAR studies on HCAs can identify the most successful antioxidants that could be useful for management of oxidative stress-related diseases.

Biogeographic and palaeoclimatic relationships of the Middle Pliocene ichthyofauna of the Samoggia Torrent (Bologna, Italy)

New Middle Pliocene ichthyofauna (2.4-2.2 Ma) from central-eastern Italy (Samoggia Torrent, Bologna) are described. These ichthyolites were found in a rather thin laminated layer that was deposited after the 2.4 Ma climatic crisis. The origin of this deposit, in which 31 taxa have been classified, is to be related to anoxic events on a regional and, probably, supraregional scale. This ichthyofaunistic association, which consists of living genera, is characterized by a clearcut predominance of mesopelagic species. The palaeoclimatic characters of these ichthyofauna indicate subtropical-type waters, while from a palaeobiogeographic point of view there is a close relationship with the present-day Atlantic-Mediterranean bioprovince. The Samoggia deposit has yielded six taxa that are absent or only occasionally present in the Mediterranean: one of these, Spratelloides gracilis, is exclusive of the Indo-Pacific bioprovince.

A hybrid genetic algorithm for the multi-mode resource-constrained project scheduling

A construction project is a group of discernible tasks or activities that are conduct-ed in a coordinated effort to accomplish one or more objectives. Construction projects re-quire varying levels of cost, time and other resources. To plan and schedule a construction project, activities must be defined sufficiently. The level of detail determines the number of activities contained within the project plan and schedule. So, finding feasible schedules which efficiently use scarce resources is a challenging task within project management. In this context, the well-known Resource Constrained Project Scheduling Problem (RCPSP) has been studied during the last decades. In the RCPSP the activities of a project have to be scheduled such that the makespan of the project is minimized. So, the technological precedence constraints have to be observed as well as limitations of the renewable resources required to accomplish the activities. Once started, an activity may not be interrupted. This problem has been extended to a more realistic model, the multi-mode resource con-strained project scheduling problem (MRCPSP), where each activity can be performed in one out of several modes. Each mode of an activity represents an alternative way of combining different levels of resource requirements with a related duration. Each renewable resource has a limited availability for the entire project such as manpower and machines. This paper presents a hybrid genetic algorithm for the multi-mode resource-constrained pro-ject scheduling problem, in which multiple execution modes are available for each of the ac-tivities of the project. The objective function is the minimization of the construction project completion time. To solve the problem, is applied a two-level genetic algorithm, which makes use of two separate levels and extend the parameterized schedule generation scheme. It is evaluated the quality of the schedules and presents detailed comparative computational re-sults for the MRCPSP, which reveal that this approach is a competitive algorithm.

A genetic algorithm for the resource constrained multi-project scheduling problem

This paper presents a genetic algorithm for the resource constrained multi-project scheduling problem. The chromosome representation of the problem is based on random keys. The schedules are constructed using a heuristic that builds parameterized active schedules based on priorities, delay times, and release dates defined by the genetic algorithm. The approach is tested on a set of randomly generated problems. The computational results validate the effectiveness of the proposed algorithm.

Genetic diversity and epidemiology of antimicrobial resistant Streptococcus pneumoniae isolates

Dissertation presented to obtain a Ph.D. degree in Biology, speciality in Microbiology, by Universidade Nova de Lisboa, Faculdade de Ciências e Tecnologia

Optimal location of supports in beam structures using genetic algorithms

Real structures can be thought as an assembly of components, as for instances plates, shells and beams. This later type of component is very commonly found in structures like frames which can involve a significant degree of complexity or as a reinforcement element of plates or shells. To obtain the desired mechanical behavior of these components or to improve their operating conditions when rehabilitating structures, one of the eventual parameters to consider for that purpose, when possible, is the location of the supports. In the present work, a beam-type structure is considered, and for a set of cases concerning different number and types of supports, as well as different load cases, the authors optimize the location of the supports in order to obtain minimum values of the maximum transverse deflection. The optimization processes are carried out using genetic algorithms. The results obtained, clearly show a good performance of the approach proposed. © 2014 IEEE.