Fine time scaling of purifying selection on human nonsynonymous mtDNA mutations based on the worldwide population tree and mother-child pairs

A high-resolution mtDNA phylogenetic tree allowed us to look backward in time to investigate purifying selection. Purifying selection was very strong in the last 2,500 years, continuously eliminating pathogenic mutations back until the end of the Younger Dryas (∼11,000 years ago), when a large population expansion likely relaxed selection pressure. This was preceded by a phase of stable selection until another relaxation occurred in the out-of-Africa migration. Demography and selection are closely related: expansions led to relaxation of selection and higher pathogenicity mutations significantly decreased the growth of descendants. The only detectible positive selection was the recurrence of highly pathogenic nonsynonymous mutations (m.3394T>C-m.3397A>G-m.3398T>C) at interior branches of the tree, preventing the formation of a dinucleotide STR (TATATA) in the MT-ND1 gene. At the most recent time scale in 124 mother-children transmissions, purifying selection was detectable through the loss of mtDNA variants with high predicted pathogenicity. A few haplogroup-defining sites were also heteroplasmic, agreeing with a significant propensity in 349 positions in the phylogenetic tree to revert back to the ancestral variant. This nonrandom mutation property explains the observation of heteroplasmic mutations at some haplogroup-defining sites in sequencing datasets, which may not indicate poor quality as has been claimed.

Level of compliance in contact lens wearing medical doctors in Nepal

PURPOSES: To determine the level of compliance and major non-compliant behaviors in contact lens (CL) wearing medical doctors (MDs) and to compare it with age matched CL wearing normal subjects with no medical background (NS). METHODS: Thirty-nine current CL wearing MDs, who were prescribed CLs in Nepal Eye Hospital, Kathmandu, Nepal, between 2007 and 2011, were interviewed on ten modifiable compliant behaviors regarding lens care and maintenance. The level of compliance and the rate of non-compliance for each behavior were determined and compared with NS. RESULTS: Level of compliance was good, average and poor in 35.9%, 48.7% and 15.4% of MDs, respectively. There was no significant difference in compliance between MDs and NS (p=0.209). Level of compliance was not associated with age, gender and duration of lens wear (p>0.05). Compliance rate varied according to different behaviors, achieving a good compliance level of 95% for hand hygiene, avoidance of water contact and not sleeping with lenses. There was poor compliance for topping up solution (53.8%) and lens case replacement (15.4%). CONCLUSION: About one third of MDs had a good level of compliance. Level of compliance and compliance rate of different behaviors were similar in MDs and NS. Periodic lens case replacement was the most neglected behavior in CL wearers for this region.

Development of procedures for the design, optimization and manufacturing of customized orthopaedic and trauma implants: Geometrical/anatomical modelling from 3D medical imaging

Tese de Doutoramento (Programa Doutoral em Engenharia Biomédica)

Longitudinal evaluation, acceptability and long-term retention of knowledge on a horizontally integrated organic and functional systems course

Undergraduate medical education is moving from traditional disciplinary basic science courses into more integrated curricula. Integration models based on organ systems originated in the 1950s, but few longitudinal studies have evaluated their effectiveness. This article outlines the development and implementation of the Organic and Functional Systems (OFS) courses at the University of Minho in Portugal, using evidence collected over 10 years. It describes the organization of content, student academic performance and acceptability of the courses, the evaluation of preparedness for future courses and the retention of knowledge on basic sciences. Students consistently rated the OFS courses highly. Physician tutors in subsequent clinical attachments considered that students were appropriately prepared. Performance in the International Foundations of Medicine examination of a self-selected sample of students revealed similar performances in basic science items after the last OFS course and 4 years later, at the moment of graduation. In conclusion, the organizational and pedagogical approaches of the OFS courses achieve high acceptability by students and result in positive outcomes in terms of preparedness for subsequent training and long-term retention of basic science knowledge.

Incorporation of antimicrobial peptides on functionalized cotton gauzes for medical applications

A large group of low molecular weight natural compounds that exhibit antimicrobial activity has been isolated from animals and plants during the past two decades. Among them, peptides are the most widespread resulting in a new generation of antimicrobial agents with higher specific activity. In the present study we have developed a new strategy to obtain antimicrobial wound-dressings based on the incorporation of antimicrobial peptides into polyelectrolyte multilayer films built by the alternate deposition of polycation (chitosan) and polyanion (alginic acid sodium salt) over cotton gauzes. Energy dispersive X ray microanalysis technique was used to determine if antimicrobial peptides penetrated within the films. FTIR analysis was performed to assess the chemical linkages, and antimicrobial assays were performed with two strains: Staphylococcus aureus (Gram-positive bacterium) and Klebsiella pneumonia (Gram-negative bacterium). Results showed that all antimicrobial peptides used in this work have provided a higher antimicrobial effect (in the range of 4 log–6 log reduction) for both microorganisms, in comparison with the controls, and are non-cytotoxic to normal human dermal fibroblasts at the concentrations tested.

Predicting SO2 pollution incidents by means of additive models with optimum variable selection

The aim of this paper is to predict time series of SO2 concentrations emitted by coal-fired power stations in order to estimate in advance emission episodes and analyze the influence of some meteorological variables in the prediction. An emission episode is said to occur when the series of bi-hourly means of SO2 is greater than a specific level. For coal-fired power stations it is essential to predict emission epi- sodes sufficiently in advance so appropriate preventive measures can be taken. We proposed a meth- odology to predict SO2 emission episodes based on using an additive model and an algorithm for variable selection. The methodology was applied to the estimation of SO2 emissions registered in sampling lo- cations near a coal-fired power station located in Northern Spain. The results obtained indicate a good performance of the model considering only two terms of the time series and that the inclusion of the meteorological variables in the model is not significant.

Spawning habitat selection by Octopus vulgaris: new insights for a more effective management of this resource

The selection of spawning habitat of a population of Octopus vulgaris that is subject to a small-scale exploitation was studied in the Cíes Islands within the National Park of the Atlantic Islands of Galicia (NW Spain). The technique used was visual censuses by scuba diving. We conducted 93 visual censuses from April 2012 to April 2014. The total swept area was 123.69 ha. Habitat features (season, depth, zone, bottom temperature, swept area, bottom substrate type, and creels fishing impact) were evaluated as predictors of the presence/absence of spawning dens using GAM models. O. vulgaris has a noteworthy preference for spawning in areas with hard bottom substrate and moderate depth (approximately 20 m). The higher density of spawning dens (1.08ha−1) was found in a surveyed area of 50.14ha located in the northeastern part of the northern Cíes Island. We propose to protect the area comprised from Punta Escodelo to Punta Ferreiro between 5 and 30 m depth. This area has a surface of 158 ha equivalent to 5.98% of the total marine area of the Cíes islands. The strengths and weaknesses of a management strategy based on the protection of the species’ spawning habitat are discussed.

Relatório de atividade profissional

Relatório de atividade profissional de mestrado em Ciências – Formação Contínua de Professores (área de especialização em Biologia e Geologia)

New integrative computational approaches unveil the Saccharomyces cerevisiae pheno-metabolomic fermentative profile and allow strain selection for winemaking

During must fermentation by Saccharomyces cerevisiae strains thousands of volatile aroma compounds are formed. The objective of the present work was to adapt computational approaches to analyze pheno-metabolomic diversity of a S. cerevisiae strain collection with different origins. Phenotypic and genetic characterization together with individual must fermentations were performed, and metabolites relevant to aromatic profiles were determined. Experimental results were projected onto a common coordinates system, revealing 17 statistical-relevant multi-dimensional modules, combining sets of most-correlated features of noteworthy biological importance. The present method allowed, as a breakthrough, to combine genetic, phenotypic and metabolomic data, which has not been possible so far due to difficulties in comparing different types of data. Therefore, the proposed computational approach revealed as successful to shed light into the holistic characterization of S. cerevisiae pheno-metabolome in must fermentative conditions. This will allow the identification of combined relevant features with application in selection of good winemaking strains.