Synthesis of polyhydroxylated compounds from Derythrose: enzymatic inhibition studies

Dissertação de mestrado em Química Medicinal

Improving selective collection of urban waste using a business intelligence system

Today recovering urban waste requires effective management services, which usually imply sophisticated monitoring and analysis mechanisms. This is essential for the smooth running of the entire recycling process as well as for planning and control urban waste recovering. In this paper we present a business intelligence system especially designed and im- plemented to support regular decision-making tasks on urban waste management processes. The system provides a set of domain-oriented analytical tools for studying and characterizing poten- tial scenarios of collection processes of urban waste, as well as for supporting waste manage- ment in urban areas, allowing for the organization and optimization of collection services. In or- der to clarify the way the system was developed and the how it operates, particularly in process visualization and data analysis, we also present the organization model of the system, the ser- vices it disposes, and the interface platforms for exploring data.

Attachment to parents: the mediating role of inhibition of exploration and individuality on health behaviors

This study’s goal was to analyze whether the quality of university students’ relationship with their parents mediated the association between mental health and physical symptoms and health behavior. Participants were 250 university students (66% female and 34% male), aged between 17 and 29 years old (M = 20.88, SD = 2.03) that answered the Father/Mother Attachment Questionnaire (FMAQ), the Physical Symptoms Scale from the Rotterdam Symptom Checklist (RSCL), the Health Behavior Questionnaire (HBQ), and the Hospital Anxiety and Depression Scale (HADS). The results showed that the indirect effect of physical symptoms on health behavior was significantly mediated by the father’s and mother’s inhibition of exploration and individuality (IEI). Also the indirect effect of psychological distress on health behavior was significantly mediated by the father’s and mother’s IEI. These results suggest that young adults who had more restrictions to their individuality show worse health behaviors. Separation Anxiety and Dependence (SAD) and Quality of Emotional Bond (QEB), the other 2 attachment scales, were not mediators of the relationship between physical symptoms/ psychological distress and health behavior. This study shows the importance of promoting positive parenting practices that contribute to healthier behavior choices and less risky behaviors, as well as the need for more studies that clearly identify these practices in young adult populations.

Extensive admixture and selective pressure across the Sahel Belt

Genome-wide studies of African populations have the potential to reveal powerful insights into the evolution of our species, as these diverse populations have been exposed to intense selective pressures imposed by infectious diseases, diet, and environmental factors. Within Africa, the Sahel Belt extensively overlaps the geographical center of several endemic infections such as malaria, trypanosomiasis, meningitis, and hemorrhagic fevers. We screened 2.5 million single nucleotide polymorphisms in 161 individuals from 13 Sahelian populations, which together with published data cover Western, Central, and Eastern Sahel, and include both nomadic and sedentary groups. We confirmed the role of this Belt as a main corridor for human migrations across the continent. Strong admixture was observed in both Central and Eastern Sahelian populations, with North Africans and Near Eastern/Arabians, respectively, but it was inexistent in Western Sahelian populations. Genome-wide local ancestry inference in admixed Sahelian populations revealed several candidate regions that were significantly enriched for non-autochthonous haplotypes, and many showed to be under positive selection. The DARC gene region in Arabs and Nubians was enriched for African ancestry, whereas the RAB3GAP1/LCT/MCM6 region in Oromo, the TAS2R gene family in Fulani, and the ALMS1/NAT8 in Turkana and Samburu were enriched for non-African ancestry. Signals of positive selection varied in terms of geographic amplitude. Some genomic regions were selected across the Belt, the most striking example being the malaria-related DARC gene. Others were Western-specific (oxytocin, calcium, and heart pathways), Eastern-specific (lipid pathways), or even population-restricted (TAS2R genes in Fulani, which may reflect sexual selection).

Monocarboxylate transport inhibition potentiates the cytotoxic effect of 5-fluorouracil in colorectal cancer cells

Cancer cells rely mostly on glycolysis to meet their energetic demands, producing large amounts of lactate that are extruded to the tumour microenvironment by monocarboxylate transporters (MCTs). The role of MCTs in the survival of colorectal cancer (CRC) cells is scarce and poorly understood. In this study, we aimed to better understand this issue and exploit these transporters as novel therapeutic targets alone or in combination with the CRC classical chemotherapeutic drug 5-Fluorouracil. For that purpose, we characterized the effects of MCT activity inhibition in normal and CRC derived cell lines and assessed the effect of MCT inhibition in combination with 5-FU. Here, we demonstrated that MCT inhibition using CHC (a-cyano-4-hydroxycinnamic acid), DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid) and quercetin decreased cell viability, disrupted the glycolytic phenotype, inhibited proliferation and enhanced cell death in CRC cells. These results were confirmed by specific inhibition of MCT1/4 by RNA interference. Notably, we showed that 5-FU cytotoxicity was potentiated by lactate transport inhibition in CRC cells, either by activity inhibition or expression silencing. These findings provide novel evidence for the pivotal role of MCTs in CRC maintenance and survival, as well as for the use of these transporters as potential new therapeutic targets in combination with CRC conventional therapy.

Protein-based nanodevices for therapeutic applications

Tese de Doutoramento em Biologia Molecular e Ambiental (área de especialização em Biologia Celular e Saúde).

Determination of catalase activity and its inhibition by a simple manometric method

[Excerpt] Introduction: There has been a considerable amount of controversy about the use of manometric methods to measure catalase activity. As Maehly and Chance point out in their excellent review] the advantages of these methods is "... that they can be used for any kind of biological material, and purification of the enzyme is not required. The assay is independent of small amounts of peroxidase activity. It is fairly simple to perform, it is rapid and it can be adapted to continuous reading of the reaction". A variety of drawbacks are also listed by the same authors, viz, the inactivation of the enzyme under the experimental conditions and the time lag before a constant rate of oxygen evolution is reached. [...]