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Biomedical subjects

R Gomes

Publications and source records attributed to R Gomes.

At least 19 recordsLinked to original sources

Can Nassarius reticulatus be used as a bioindicator for Hg contamination? Results from a longitudinal study of the Portuguese coastline.

The focus of this work is to explore the use of the netted whelk, Nassarius reticulatus (L.), as an indicator of mercury (Hg) contamination, by assessing the concentration of Hg in the sediments and in the whelk along the entire Portuguese coast. Total Hg concentrations ranged from below the detection limit (0.01 ng absolute mercury) up to 0.87 mg kg(-1) dry weight (dwt) in sediments and between 0.06 and 1.02 mg kg(-1) (dwt) for organisms, with no significant differences between males and females. Although organic mercury was not detected in the sediments, it represented, on average, 52% of the total Hg in the whelk tissues, and as high as 88% in some cases, suggesting mercury accumulation from dietary intake. Significant negative correlations were found between the total Hg concentrations in the sediments and the log(10) of Hg concentrations in whelk tissues males (r=-0.64; P<0.01) and females (r=-0.52; P<0.01) indicating that the species is a poor indicator of Hg contamination. Nevertheless, since the highest concentrations of organic mercury in the whelk tissues were found in the least contaminated areas, this species must be highly relevant in the trophic web, namely on the possible biomagnification of mercury. The high dietary mercury accumulation from feeding on carrion and the low bioavailability of mercury to whelks in estuarine sediments may be the basis of the mercury accumulation pattern in N. reticulatus.

Animals↗

Origin of the orbital architecture of the giant planets of the Solar System.

Planetary formation theories suggest that the giant planets formed on circular and coplanar orbits. The eccentricities of Jupiter, Saturn and Uranus, however, reach values of 6 per cent, 9 per cent and 8 per cent, respectively. In addition, the inclinations of the orbital planes of Saturn, Uranus and Neptune take maximum values of approximately 2 degrees with respect to the mean orbital plane of Jupiter. Existing models for the excitation of the eccentricity of extrasolar giant planets have not been successfully applied to the Solar System. Here we show that a planetary system with initial quasi-circular, coplanar orbits would have evolved to the current orbital configuration, provided that Jupiter and Saturn crossed their 1:2 orbital resonance. We show that this resonance crossing could have occurred as the giant planets migrated owing to their interaction with a disk of planetesimals. Our model reproduces all the important characteristics of the giant planets' orbits, namely their final semimajor axes, eccentricities and mutual inclinations.

Journal Article↗

Chaotic capture of Jupiter's Trojan asteroids in the early Solar System.

Jupiter's Trojans are asteroids that follow essentially the same orbit as Jupiter, but lead or trail the planet by an angular distance of approximately 60 degrees (co-orbital motion). They are hypothesized to be planetesimals that formed near Jupiter and were captured onto their current orbits while Jupiter was growing, possibly with the help of gas drag and/or collisions. This idea, however, cannot explain some basic properties of the Trojan population, in particular its broad orbital inclination distribution, which ranges up to approximately 40 degrees (ref. 8). Here we show that the Trojans could have formed in more distant regions and been subsequently captured into co-orbital motion with Jupiter during the time when the giant planets migrated by removing neighbouring planetesimals. The capture was possible during a short period of time, just after Jupiter and Saturn crossed their mutual 1:2 resonance, when the dynamics of the Trojan region were completely chaotic. Our simulations of this process satisfactorily reproduce the orbital distribution of the Trojans and their total mass.

Journal Article↗

Origin of the cataclysmic Late Heavy Bombardment period of the terrestrial planets.

The petrology record on the Moon suggests that a cataclysmic spike in the cratering rate occurred approximately 700 million years after the planets formed; this event is known as the Late Heavy Bombardment (LHB). Planetary formation theories cannot naturally account for an intense period of planetesimal bombardment so late in Solar System history. Several models have been proposed to explain a late impact spike, but none of them has been set within a self-consistent framework of Solar System evolution. Here we propose that the LHB was triggered by the rapid migration of the giant planets, which occurred after a long quiescent period. During this burst of migration, the planetesimal disk outside the orbits of the planets was destabilized, causing a sudden massive delivery of planetesimals to the inner Solar System. The asteroid belt was also strongly perturbed, with these objects supplying a significant fraction of the LHB impactors in accordance with recent geochemical evidence. Our model not only naturally explains the LHB, but also reproduces the observational constraints of the outer Solar System.

Journal Article↗

Methanol induction optimization for scFv antibody fragment production in Pichia pastoris.

Fibronectin splice variant ED B (extracellular domain B) is a promising marker for angiogenesis in growing solid tumors. Currently, recombinant antibodies against ED B are being investigated concerning their potential use, for either therapeutic or diagnostic purposes. Single-chain antibody fragments directed against the ED B can be efficiently expressed in Pichia pastoris; thus, a recombinant strain of the methylotropic yeast P. pastoris was used for this work. Three different forms of scFv antibody fragment are found in the supernatant from this fermentation: covalent homodimer, associative homodimer, and monomer. Both homodimeric forms can be converted to the monomeric form (under reducing conditions) and be efficiently radiolabeled, whereas the monomeric form of scFv already present in the supernatant cannot. It was also found that the fraction of protein in the monomeric form is highly dependent on the mode of induction rather than scFv concentration. This suggests that the monomeric form of the scFv present in the supernatant might be a result of events occurring at the expression, secretion, or folding level. A high cell density fermentation protocol was developed by optimizing methanol induction, yielding the highest scFv antibody fragment production rate and product quality; cell concentration at the induction point and specific methanol uptake rate were found to be the most important control variables. A decrease in specific methanol uptake rate led to a higher specific production rate for the scFv antibody fragment (5.4 microg g(cell) h(-1)). Product quality, i.e., percentage of product in a homodimeric form, also increased with the decrease in methanol uptake rate. Furthermore, the volumetric productivity depended on cell concentration at the induction point, increasing with the increase of cell concentration up to 320 g L(-1) wet cell weight (WCW). The reduction of the methanol feeding rate for induction, and consequently of the oxygen uptake rate, have important consequences for optimizing product titers and quality and thus on the scale-up of this production process; hence one of the major limitations upon high cell density cultivation in bioreactors is keeping the high oxygen transfer rate required. From the results obtained, a scale-up strategy was developed based on the available oxygen transfer rates at larger scales, allowing the definition of the optimum biomass concentration for induction and methanol feeding strategy for maximization of product titer and quality.

Cell Division↗

[Child prostitution: a public health issue].

This article analyzes child prostitution based on a review of the literature, in order to support an approach to this problem by the field of Public Health. First, health, prostitution, and violence are discussed as categories. Prostitution has traditionally been analyzed from a medical perspective, mostly within a hygienist point of view. However, the issue is dealt with here from a different perspective. After this discussion, several aspects about the cruelty of Brazilian reality are revealed showing that prostitution among children and teenagers is a way of survival. From this angle, poverty and child prostitution are closely related, although the study concludes that the latter is not solely a consequence of the former. Over the course of the review, a number of publications on the current issue are taken into consideration in order to best contribute to the discussion of the matter. Finally, the author concludes that to confront this problem it must be considered within the family context and linked to macro-social questions.

English Abstract↗

Anti-glycation defences in yeast.

Saccharomyces cerevisiae is an outstanding cellular model for metabolic studies in glycation. Due to its high glycolytic activity, it produces methylglyoxal, a highly reactive intracellular glycation agent, at a rate of approx. 0.1% of the glycolytic flux. We investigated methylglyoxal metabolism in Saccharomyces cerevisiae cells, using haploid null mutants. Growth studies showed that the most sensitive strains to 2-oxoaldehydes were the null mutants for GSH1 and GLO1, coding for glutathione synthase I and glyoxalase I respectively. The GRE3 null mutant, lacking aldose reductase activity, is as sensitive as the control strain. Kinetic modelling and computer simulation of this type of experiment were also performed, and we concluded that the most important parameters for controlling the intracellular concentration of methylglyoxal are the activity of glyoxalase I and the GSH concentration. Moreover, our model predicts an intracellular steady-state concentration of methylglyoxal of approx. 2 microM. Our results show that the glyoxalase pathway is the main detoxification pathway for 2-oxoaldehydes in yeast, and is likely to be the key enzymatic anti-glycation agent in these cells.

Glucose↗

Genetic variation in populations of Leishmania species in Brazil.

The population structure of strains of Leishmania (Viannia) braziliensis sensu lato from Pará State and Paraná State in Brazil, of L. (V.) shawi and L. (Leishmania) amazonensis from Pará State, and the relationships of type strains of the subgenera L. (Viannia) and L. (Leishmania) were examined by the random-amplified polymorphic deoxyribonucleic acid (RAPD) technique. Four different primers (M13-40, QG1, L15996 and delta gt11R) were used. The bands were analysed using the neighbor-joining (NJ) and unweighted pair-group method with arithmetic averages (UPGMA) algorithms of the MEGA package. The topology of the NJ and UPGMA trees was very similar but they were not always identical. Both trees differentiated the standard strains of the different species. Strains from the same location were grouped together only in the UPGMA phenogram of the M13-40 primer. L. (V.) braziliensis isolates from Paraná State were genetically closer to those from Paragominas, Pará State than to those from the Amazonian regions of Carajás in Pará State and Peru. The relationship was not dependent on geographical distance. It is postulated that the groups arose from different origins, in which the Amazonian stocks were related to Psychodopygus sand flies while the Paraná strains originated from a gene pool transmitted by Lutzomyia sand flies such as Lutzomyia (Nyssomyia) whitmani. Transmission by Ps. complexus in Paragominas is considered to be a secondary adaptation from the Lutzomyia leishmanial gene pool. Although the vectors of L. (V.) braziliensis are poorly known in the Amazon region, there is strong evidence that the major vectors are all Psychodopygus spp. There was a high degree of genetic variability amongst the L. (V.) shawi strains and there was no clear grouping according to the strains' origins. The genetic variability amongst L. (L.) amazonensis strains from the same locations was much lower but they formed 2 groups which coincided with their origin. Our results support the clonal population structure of Leishmania isolates and suggest that their distribution is related to the origin of the gene pool as well as to present vector and reservoir movements.

Animals↗

Perlecan: an important component of the cartilage pericellular matrix.

Perlecan (Pln) is a large proteoglycan that can bear HS (heparan sulfate) and chondroitin sulfate glycosaminoglycans. Previous studies have demonstrated that Pln can interact with growth factors and cell surfaces either via its constituent glycosaminoglycan chains or core protein. Herein, we summarize studies demonstrating spatially and temporally regulated expression of Pln mRNA and protein in developing and mature cartilage. Mutations either in the Pln gene or in genes involved in glycosaminoglycan assembly result in severe cartilage phenotypes seen in both human syndromes and mouse model systems. In vitro studies demonstrate that Pln can trigger chondrogenic differentiation of multipotential mouse CH310T1/2 stem cells as well as maintain the phenotype of adult human chondrocytes. Structural mapping indicates that these activities lie entirely within domain I, a region unique to Pln, and that they require glycosaminoglycans. We also discuss data indicating that Pln cooperates with the key chondrogenic growth factor, BMP-2, to promote expression of hypertrophic chondrocyte markers. Collectively, these studies indicate that Pln is an important component of human cartilage and may have useful applications in tissue engineering and cartilage-directed therapeutics.

Journal Article↗

Greater velocity and magnitude of airway narrowing in immature than in mature rabbit lung explants.

Methacholine (MCh)-induced bronchoconstriction in vivo produces greater maximal increases in pulmonary and airway resistances in immature than in mature rabbits. Our recent findings of lower shear modulus and greater airway distensibility suggest a lower elastic load limiting airway smooth muscle (ASM) shortening in immature rabbit lungs. We hypothesized that a lower elastic load should result in greater velocity of airway narrowing. Lung explants were prepared from three immature and five mature rabbits. Dynamic narrowing of intraparenchymal airways after maximal MCh stimulation was assessed by video microscopy. Immature airways (n = 80) compared with mature airways (n = 110) demonstrated greater peak velocity of shortening (6.98 +/- 0.32 versus 4.22 +/- 0.18% of baseline perimeter/s) and greater maximal airway narrowing, expressed as percentage of baseline area (31.9 +/- 1.6 versus 42.2 +/- 1.8%). For both groups, a greater velocity of shortening resulted in greater airway narrowing. As available data do not support maturational differences in rabbit ASM, our results are consistent with a lower elastic load limiting ASM shortening in the immature rabbit.

Age Factors↗

[The meaning of sexuality for adolescents living in the streets of Goiania].

This study aimed at reflecting on the sexuality for adolescents living on the street, based on their point of view. Authors used a qualitative approach in order to identify general aspects related to the sexuality of adolescents living on the street in Goiânia. Data were collected through semi-structured interviews and participant observation. Results showed that these adolescents consider the sexuality reduced to the sexual act, and that even on the streets they are not deprived of it. Also, the prevention is a practically non-existent attitude in their daily life. Thus, authors pointed out the importance of nurses commitment to that group through health education and promotion.

Adolescent↗

[Meanings of risk in pregnancy according to obstetrics: bibliographic study].

This study analyzes the meaning of high-risk pregnancy in articles published by a representative Brazilian journal in the field of Obstetrics in the 1990s. The methodological approach includes the quantitative and qualitative analysis of 40 articles, which reveals a diversity of meanings attributed to high-risk pregnancy and a reduced discussion on the theme. The conclusion shows the need to include an interdisciplinary approach to the theme by taking into account the complexity of the aspects involving women's participation in pregnancy care.

Bibliometrics↗

Rough deal and Zw10 are required for the metaphase checkpoint in Drosophila.

The metaphase-anaphase transition during mitosis is carefully regulated in order to assure high-fidelity transmission of genetic information to the daughter cells. A surveillance mechanism known as the metaphase checkpoint (or spindle-assembly checkpoint) monitors the attachment of kinetochores to the spindle microtubules, and inhibits anaphase onset until all chromosomes have achieved a proper bipolar orientation on the spindle. Defects in this checkpoint lead to premature anaphase onset, and consequently to greatly increased rates of aneuploidy. Here we show that the Drosophila kinetochore components Rough deal (Rod) and Zeste-White 10 (Zw10) are required for the proper functioning of the metaphase checkpoint in flies. Drosophila cells lacking either ROD or Zw10 exhibit a phenotype that is similar to that of bub1 mutants - they do not arrest in metaphase in response to spindle damage, but instead separate sister chromatids, degrade cyclin B and exit mitosis. These are the first checkpoint components to be identified that do not have obvious homologues in budding yeast.

Animals↗

Bronchial responsiveness among inbred mouse strains. Role of airway smooth-muscle shortening velocity.

To investigate the relationship between bronchial responsiveness and airway smooth-muscle (ASM) contractile properties, we studied inbred mice with known interstrain differences in airway responsiveness. Using oscillatory mechanics, we confirmed that A/J mice were hyperresponsive to methacholine (MCh) as compared with mice of the C3H/HeJ and C57BL/6J strains. Analysis of respiratory system resistance and elastance at different flow oscillation frequencies indicated that interstrain differences in responsiveness are present in both central and peripheral airways of these mice. We used video microscopy to measure the rate of contraction of explanted airways, and found that the airways of A/J mice contracted more rapidly than those of C3H/HeJ or C57BL/6J mice. In studies of a fourth strain (Balb/C) of mice, we found both bronchial hyperresponsiveness and increased ASM shortening velocity. The rank order of responsiveness among strains was the same as that for shortening velocity (A/J > Balb/C > C3H/HeJ > C57BL/6J). Furthermore, in each strain of mice, shortening velocity correlated with the achieved degree of airway narrowing and with a greater likelihood of airway closure in individual airways. In contrast, generation of isometric tension in trachealis, morphometric measurements of tracheal ASM, tracheal myosin content, and dose-response curves for MCh of explanted intraparenchymal bronchi failed to correspond to the in vivo phenotype of airway reactivity. These results indicate that bronchial responsiveness is related to ASM shortening velocity, and underscore the importance of smooth-muscle dynamics in understanding the mechanisms of bronchial responsiveness.

Airway Resistance↗

[Sexuality in adolescence: a bibliographic study].

This is a bibliographical study that aimed at pointing out the history of sexuality as well as its cultural, social and religious influences. The goals were to find out in literature the causes of the difficulties faced by the actual men to approach themes related to sexuality mainly with their adolescent children that need this orientation in order to live a safer and healthier sexuality.

Adolescent↗

P-glycoprotein phosphorylation/dephosphorylation and cellular accumulation of L-DOPA in LLC-GA5 Col300 cells.

1. The present work was aimed to study the effect of PKC activation and protein-serine/threonine phosphatase (PP1/PP2 A) inhibition on P-glycoprotein (P-gp) mediated transport of L-DOPA in LLC-GA5 Col300 cells, a renal cell line expressing the human P-glycoprotein in the apical membrane. 2. L-DOPA accumulation was a time-and concentration-dependent process with the following kinetic characteristics: kin, 57.3 +/- 1.2 pmol mg protein(-1) min(-1); k(out), 3.3 +/- 0.1 pmol mg(-1) protein min(-1); Amax, 10.6 +/- 0.8; Kn, 198 +/- 64 microM; Vmax, 5.2 +/- 0.7 nmol mg protein(-1). 3. Verapamil (25 microM), a P-glycoprotein inhibitor, markedly increased (approximately 40% increase) the accumulation of a non-saturating concentration of L-DOPA (2.5 microM) at both initial rate of uptake (IRU, 6 min incubation) and at steady-state (SS, 30 min incubation). 4. PKC activation with phorbol 12,13-dibutyrate (PDBu, 1, 3 and 10 nM) produced a concentration-dependent decrease in L-DOPA accumulation at SS, but not at IRU. The inactive phorbol ester, 4alpha-phorbol 12,13-didecanoate (100 nM), produced no change in L-DOPA accumulation. The effect of PDBu was completely reverted by staurosporine (100 nM). The phosphatase inhibitor okadaic acid (100 nM) reduced by 20% the accumulation of L-DOPA at IRU, but not at SS. 5. It is suggested that P-glycoprotein plays a role in regulation of intracellular availability of L-DOPA in renal epithelial cells, and phosphorylation/dephosphorylation of P-glycoprotein may be involved in the regulation of the transporter.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Potential mechanisms for the plasmin-mediated release and activation of latent transforming growth factor-beta1 from the extracellular matrix of growth plate chondrocytes.

Chondrocytes produce latent transforming growth factor-beta1 (TGF-beta1) in a small, circulating form of 100 kDa and also store latent TGF-beta1 in their matrix in a large form of 290 kDa containing the latent TGF-beta1 binding protein 1. As growth plate cartilage cells are exceptionally sensitive to TGF-beta1 and are known to produce plasminogen activator, the role of plasmin in the activation of soluble and matrix-bound latent TGF-beta1 was examined. As is true for other cell types, low-dose plasmin (0.01 U/ml) was found to release both active and latent TGF-beta1 from chondrocyte matrix in a time-dependent manner over 3 h. However, high-dose plasmin (1.0 U/ml) was found to release active TGF-beta1 more rapidly than low-dose plasmin, and this release ceased within 30 min; latent complex continued to be released over time (3 h). When high-dose plasmin was titrated against the serine protease inhibitors, aprotinin and alpha-(2-aminoethyl)benzenesulfonyl fluoride, results similar to low-dose plasmin were obtained, indicating that the effects of high-dose plasmin could be altered to mimic those of low-dose plasmin. No differences were observed on the effects of plasmin on the release of TGF-beta1 from the matrices of either growth zone or resting zone chondrocytes. We examined whether plasmin could further activate the truncated large latent TGF-beta1 complex of 230 kDa that was released into the media by plasmin. It is known that plasmin will activate the small latent complex, so this was compared with the truncated form. Plasmin completely activated the small latent complex, whereas a smaller, but significant, activation of the truncated form of latent TGF-beta1 also occurred. These studies may have relevance to normal physiological conditions, where plasminogen and/or plasmin is present in very small amounts in the cartilage and, therefore, small amounts of active TGF-beta1 would be present, and to pathological conditions such as fractures, where chondroprogenitor cells would be exposed to high concentrations of plasmin and, therefore, to short-term high concentrations of this potent chondrogenic growth factor.

Animals↗