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.

Caracterização de um mamógrafo Senographe 600T Senix da GE com ânodo de Mo. dosimetria das qualidades de radiação

Dissertação para obtenção do Grau de Mestre em Engenharia Biomédica

The PROP1 2-Base Pair Deletion Is a Common Cause of Combined Pituitary Hormone Deficiency

Combined pituitary hormone deficiency (CPHD) has an incidence of approximately 1 in 8000 births. Although the proportion of familial CPHD cases is unknown, about 10% have an affected first degree relative. We have recently reported three mutations in the PROP1 gene that cause CPHD in human subjects. We report here the frequency of one of these mutations, a 301–302delAG deletion in exon 2 of PROP1, in 10 independently ascertained CPHD kindreds and 21 sporadic cases of CPHD from 8 different countries. Our results show that 55% (11 of 20) of PROP1 alleles have the 301–302delAG deletion in familial CPHD cases. Interestingly, although only 12% (5 of 42) of the PROP1 alleles of our 21 sporadic cases were 301–302delAG, the frequency of this allele (in 20 of 21 of the sporadic subjects given TRH stimulation tests) was 50% (3 of 6) and 0% (0 of 34) in the CPHD cases with pituitary and hypothalamic defects, respectively. Using whole genome radiation hybrid analysis, we localized the PROP1 gene to the distal end of chromosome 5q and identified a tightly linked polymorphic marker, D5S408, which can be used in segregation studies. Analysis of this marker in affected subjects with the 301–302delAG deletion suggests that rather than being inherited from a common founder, the 301–302delAG may be a recurring mutation.

The PROP1 2-Base Pair Deletion Is a Common Cause of Combined Pituitary Hormone Deficiency

Combined pituitary hormone deficiency (CPHD) has an incidence of approximately 1 in 8000 births. Although the proportion of familial CPHD cases is unknown, about 10% have an affected first degree relative. We have recently reported three mutations in the PROP1 gene that cause CPHD in human subjects. We report here the frequency of one of these mutations, a 301-302delAG deletion in exon 2 of PROP1, in 10 independently ascertained CPHD kindreds and 21 sporadic cases of CPHD from 8 different countries. Our results show that 55% (11 of 20) of PROP1 alleles have the 301-302delAG deletion in familial CPHD cases. Interestingly, although only 12% (5 of 42) of the PROP1 alleles of our 21 sporadic cases were 301-302delAG, the frequency of this allele (in 20 of 21 of the sporadic subjects given TRH stimulation tests) was 50% (3 of 6) and 0% (0 of 34) in the CPHD cases with pituitary and hypothalamic defects, respectively. Using whole genome radiation hybrid analysis, we localized the PROP1 gene to the distal end of chromosome 5q and identified a tightly linked polymorphic marker, D5S408, which can be used in segregation studies. Analysis of this marker in affected subjects with the 301-302delAG deletion suggests that rather than being inherited from a common founder, the 301-302delAG may be a recurring mutation.

Héraldique des sceaux du clergé séculier portugais au Moyen Âge

Ce n’est que dans les dernières années que l’héraldique au Portugal a entamé le processus de rénovation qui, en France, a commencé il y a déjà quelques décennies. Dans ce processus, l’étude de l’héraldique médiévale a été peu contemplé, restant pratiquement à faire, en bonne partir dû à l’absence d’armoriaux antérieurs au XVe siècle qui permettent de connaître les armes utilisées par les familles et les diverses entités portugaises. Pour cette raison, les sceaux portant des représentations héraldiques ont une importance extrême, car ils constituent très fréquemment la seule source pour l’étude des armoiries, ayant en plus l’avantage d’être datés avec précision et liées à des personnages ou entités qui sont connues. Cependant, la sigillographie portugaise se trouve aussi dans une phase de son évolution qui, n’étant plus embryonnaire, est encore une phase de formation. Il nous manque des catalogues, des dépouillages systématiques, des études approfondies qui permettent aux héraldistes de faire leurs recherches. C’est dans ce contexte qui est née ce partenariat entre deux médiévalistes très intéressés à la sigillographie et un spécialiste d’héraldique, qui ensemble ont décidé d’entamer l’étude des origines des représentations héraldiques dans les sceaux portugais, en commençant par les sceaux du clergé séculier, qui constitue le sujet par excellence de la recherche des deux historiens. Dans ce vaste univers sigillaire, qui concerne des personnes d’une grande variété d’origines sociales, y compris la noblesse et la riche bourgeoisie urbaine, les éléments héraldiques semblent avoir émergé seulement à partir de la fin du XIIIe siècle, et d’une façon timide. Le XIVe siècle assiste à sa diffusion dans les sceaux d’évêques, dignités et chanoines, mais ce n’est qu’au XVe siècle que l’héraldique s’impose, gagnant même une place primordiale dans quelques représentations sigillographiques. Le but de cette communication sera donc l’analyse du processus d’héraldisation des sceaux du clergé séculier portugais, entre les dernières décennies du XIIIe et le XVe siècle, pour évaluer comme s’est procédé, dans le cas portugais, le phénomène d’«acculturation héraldique» de l’emblématique épiscopale et cléricale.

Petites villes européenes au bas Moyen Âge: perspectives de recherche

Fundação para a Ciência e Tecnologia,

BÉRIOU, Nicole, JOSSERAND, Philippe (coord.), Prier et Combattre – Dictionnaire européen des ordres militaires au Moyen Âge, Fayard, 2009

Medievalista [Em linha]. Nº10, (Julho 2011). Direc. José Mattoso. Lisboa: IEM.

Arterial Hypertension in a Child with Williams-Beuren Syndrome (7q11.23 Chromosomal Deletion)

We report the case of a 7-year-old male child diagnosed with Williams-Beuren syndrome and arterial hypertension refractory to clinical treatment. The diagnosis was confirmed by genetic study. Narrowing of the descending aorta and stenosis of the renal arteries were also diagnosed. Systemic vascular alterations caused by deletion of the elastin gene may occur early in individuals with Williams-Beuren syndrome, leading to the clinical manifestation of systemic arterial hypertension refractory to drug treatment.

Xenia orchidacea :Beiträge zur Kenntniss der Orchideen /von Heinrich Gustav Reichenbach fil.

1858 v. 1

Xenia orchidacea :Beiträge zur Kenntniss der Orchideen /von Heinrich Gustav Reichenbach fil.

1874 v. 2

Xenia orchidacea :Beiträge zur Kenntniss der Orchideen /von Heinrich Gustav Reichenbach fil.

1900 v. 3

Congenital Heart Disease as a Warning Sign for the Diagnosis of the 22q11.2 Deletion

Background: To alert for the diagnosis of the 22q11.2 deletion syndrome (22q11.2DS) in patients with congenital heart disease (CHD). Objective: To describe the main CHDs, as well as phenotypic, metabolic and immunological findings in a series of 60 patients diagnosed with 22q11.2DS. Methods: The study included 60 patients with 22q11.2DS evaluated between 2007 and 2013 (M:F=1.3, age range 14 days to 20 years and 3 months) at a pediatric reference center for primary immunodeficiencies. The diagnosis was established by detection of the 22q11.2 microdeletion using FISH (n = 18) and/or MLPA (n = 42), in association with clinical and laboratory information. Associated CHDs, progression of phenotypic facial features, hypocalcemia and immunological changes were analyzed. Results: CHDs were detected in 77% of the patients and the most frequent type was tetralogy of Fallot (38.3%). Surgical correction of CHD was performed in 34 patients. Craniofacial dysmorphisms were detected in 41 patients: elongated face (60%) and/or elongated nose (53.3%), narrow palpebral fissure (50%), dysplastic, overfolded ears (48.3%), thin lips (41.6%), elongated fingers (38.3%) and short stature (36.6%). Hypocalcemia was detected in 64.2% and decreased parathyroid hormone (PTH) level in 25.9%. Decrease in total lymphocytes, CD4 and CD8 counts were present in 40%, 53.3% and 33.3%, respectively. Hypogammaglobulinemia was detected in one patient and decreased concentrations of immunoglobulin M (IgM) in two other patients. Conclusion: Suspicion for 22q11.2DS should be raised in all patients with CHD associated with hypocalcemia and/or facial dysmorphisms, considering that many of these changes may evolve with age. The 22q11.2 microdeletion should be confirmed by molecular testing in all patients.