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.

Coexistencia de variantes HIV-1 com insercao dipeptidica no gene da transcriptase reversa

O objetivo desta comunicação foi descrever a detecção de coexistência de variantes HIV-1 com inserções de dois aminoácidos entre os códons 69 e 70 da transcriptase reversa. Tais variantes foram isoladas de paciente do sexo masculino, 16 anos de idade, em tratamento no interior do estado de São Paulo. Após confirmação de falha terapêutica, foi realizado teste de resistência a antirretrovirais, a partir do qual foram detectadas duas variantes contendo inserções dos aminoácidos Ser-Gly/Ser-Ala no códon 69 da transcriptase reversa, além da mutação T69S. Tais inserções possuem baixa prevalência, não foram relatadas em caráter de coexistência no Brasil e estão relacionadas com a resistência a múltiplas drogas, tornando o achado relevante do ponto de vista epidemiológico.

Physiotherapy and Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is a severe, progressive disease first described by Meryon in 1852 and later by Guillaume Duchene. It is the most common and severe form of childhood muscular dystrophy, affecting 1 in 3500 live male births. Is caused by an X—linked recessive genetic disorder resulting in a deficiency of the dystrophin protein, responsible for linking contractile proteins to the sarcolemma. Diagnosis is not always easy and the first symptoms are often related to weakness and difficulty or delay in acquiring the ability to perform simple activities. Progressive weakness leads to the use of compensatory strategies in order to maintain the ability to walk and perform other activities. Respiratory muscles are also affected and the complications resulting from its impairments are frequently the cause of early death of these patients. The advances in DMD management has increased life expectancy of these children with the need for adequate care in adulthood. DMD manifestations include muscle weakness, contractures, respiratory and cardiac complications. Some authors also refer that one-third of patients have difficulties with learning and delayed global development because the gene that encodes dystrophyn expresses various dystrophin isoforms that are found in Schwann and Purkinje celis in the brain. Body functions and structure impairments like muscle weakness, contractures and reduced range of motion lead to limitations in activities, i.e., impairments affect the performance of tasks by the individual. In a physiotherapist’s point of view analysing these limitations is mandatory because physiotherapy’s final purpose is to restore or preserve the ability to perform ADL and to improve quality of life.

Polimorfismos da região da integrase, do gene pol, em doentes infectados por VIH-1

Ciências biomédicas

Transformation of Medicago truncatula with the arginine decarboxylase gene to modify polyamine metabolism toward water deficit resistance

Dissertation submitted to obtain a Ph.D. (Doutoramento) degree in Biology at the Instituto de Tecnologia Química e Biológica da Universidade Nova de Lisboa

Gammaretroviral and lentiviral vectors for gene therapy: stability and inactivation mechanisms

Dissertation presented to obtain a Ph.D degree in Engineering and Technology Sciences, Gene Therapy at the Instituto de Tecnologia Quimica e Biológica, Universidade Nova de Lisboa

Post-transcriptional regulation of HFE gene expression

Thesis presented to obtain the Ph.D. degree in Biology (Molecular Genetics), by the Universidade Nova de Lisboa, Faculdade de Ciências e Tecnologia.

Rapid Evolution of the Sequences and Gene Repertoires

Proteins secreted to the extracellular environment or to the periphery of the cell envelope, the secretome, play essential roles in foraging, antagonistic and mutualistic interactions. We hypothesize that arms races, genetic conflicts and varying selective pressures should lead to the rapid change of sequences and gene repertoires of the secretome. The analysis of 42 bacterial pan-genomes shows that secreted, and especially extracellular proteins, are predominantly encoded in the accessory genome, i.e. among genes not ubiquitous within the clade. Genes encoding outer membrane proteins might engage more frequently in intra-chromosomal gene conversion because they are more often in multi-genic families. The gene sequences encoding the secretome evolve faster than the rest of the genome and in particular at non-synonymous positions. Cell wall proteins in Firmicutes evolve particularly fast when compared with outer membrane proteins of Proteobacteria. Virulence factors are over-represented in the secretome, notably in outer membrane proteins, but cell localization explains more of the variance in substitution rates and gene repertoires than sequence homology to known virulence factors. Accordingly, the repertoires and sequences of the genes encoding the secretome change fast in the clades of obligatory and facultative pathogens and also in the clades of mutualists and free-living bacteria. Our study shows that cell localization shapes genome evolution. In agreement with our hypothesis, the repertoires and the sequences of genes encoding secreted proteins evolve fast. The particularly rapid change of extracellular proteins suggests that these public goods are key players in bacterial adaptation.

Linking the embryonic clock with temporal collinearity of Hox gene activation

Dissertação apresentada para a obtenção do Grau de Mestre em Genética Molecular e Biomedicina, pela Universidade Nova de Lisboa, Faculdade de Ciências e Tecnologia

Novel Secretion Apparatus Maintains Spore Integrity and Developmental Gene Expression in Bacillus subtilis

Plos Genetics, 5(7): ARTe1000566

Establishing a high titer transient gene expression process in conditioned media for CHO-DG44 cells

Dissertação para obtenção do Grau de Mestre em Biotecnologia

Gold nanoparticle-DNA conjugates for oligonucleotide vectorization towards gene silencing

Dissertação para obtenção do Grau de Mestre em Genética Molecular e Biomedicina

Juvenile Parkinson disease caused by parkin mutations: large deletions and pathogenic mechanisms

Dissertação para obtenção do Grau de Mestre em Genética Molecular e Biomedicina

Mapping of a Leishmania major gene/locus that confers pentamidine resistance by deletion and insertion of transposable element

Pentamidine (PEN) is an alternative compound to treat antimony-resistant leishmaniasis patients, which cellular target remains unclear. One approach to the identification of prospective targets is to identify genes able to mediate PEN resistance following overexpression. Starting from a genomic library of transfected parasites bearing a multicopy episomal cosmid vector containing wild-type Leishmania major DNA, we isolated one locus capable to render PEN resistance to wild type cells after DNA transfection. In order to map this Leishmania locus, cosmid insert was deleted by two successive sets of partial digestion with restriction enzymes, followed by transfection into wild type cells, overexpression, induction and functional tests in the presence of PEN. To determine the Leishmania gene related to PEN resistance, nucleotide sequencing experiments were done through insertion of the transposon Mariner element of Drosophila melanogaster (mosK) into the deleted insert to work as primer island. Using general molecular techniques, we described here this method that permits a quickly identification of a functional gene facilitating nucleotide sequence experiments from large DNA fragments. Followed experiments revealed the presence of a P-Glycoprotein gene in this locus which role in Leishmania metabolism has now been analyzed.