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Biomedical subjects

G G Pereira

Publications and source records attributed to G G Pereira.

13 recordsLinked to original sources

Semiflexible grafted polymers in poor solvents: toroidal, archway, and tower micelles.

We study a system of grafted semiflexible polymers in a poor solvent which form toroidal or rodlike conformations in the bulk. However, because of the physical constraint of surface grafting, macrophase separation is inhibited and a number of different polymer aggregates (or micelles) form which can be related to the chains' stiffness and their affinity for each other. In contrast to the fully flexible Gaussian case, we observe a number of novel micelle structures, including tower micelles, archway micelles, and spider micelles. We also attempt to develop a phase diagram for the occurrence of these structures with respect to the variables of chain length, chain stiffness, and polymer grafting density.

Journal Article↗

Morphological structures formed by grafted polymers in poor solvents.

We study a system of grafted polymers in a poor solvent by self-consistent-field methods as well as Monte-Carlo simulation methods. We observe a number of different morphological structures including an inverted solvent micelle or hole in the polymer layer, a lamella-like micelle structure, and fused, spherical micelle structures. These structures can be obtained by either varying the grafting density or chain length. We also develop a scaling theory for the existence of these structures and find reasonable agreement between this theory and our numerical calculations.

Journal Article↗

Semiflexible polymer condensates in poor solvents: toroid versus spherical geometries.

Semiflexible polymers, such as DNA, in the presence of a condensing agent often form toroids. This is due to a balance between bending and surface area free energy penalties. Here we show why in experiments all the toroids have been found to have similar physical size. We also introduce a novel morphology, that of the hollow sphere, which is favored for long polymer chains. This offers the possibility of encapsulating material inside a "vesicle" made of semiflexible polymers. We also consider the case of many such polymer chains placed in a poor solvent. We show a transition between two morphologies occur on increasing concentration of polymer chains, from a thickened toroid to a spherical globule.

Journal Article↗

Comparative genomics of two Leptospira interrogans serovars reveals novel insights into physiology and pathogenesis.

Leptospira species colonize a significant proportion of rodent populations worldwide and produce life-threatening infections in accidental hosts, including humans. Complete genome sequencing of Leptospira interrogans serovar Copenhageni and comparative analysis with the available Leptospira interrogans serovar Lai genome reveal that despite overall genetic similarity there are significant structural differences, including a large chromosomal inversion and extensive variation in the number and distribution of insertion sequence elements. Genome sequence analysis elucidates many of the novel aspects of leptospiral physiology relating to energy metabolism, oxygen tolerance, two-component signal transduction systems, and mechanisms of pathogenesis. A broad array of transcriptional regulation proteins and two new families of afimbrial adhesins which contribute to host tissue colonization in the early steps of infection were identified. Differences in genes involved in the biosynthesis of lipopolysaccharide O side chains between the Copenhageni and Lai serovars were identified, offering an important starting point for the elucidation of the organism's complex polysaccharide surface antigens. Differences in adhesins and in lipopolysaccharide might be associated with the adaptation of serovars Copenhageni and Lai to different animal hosts. Hundreds of genes encoding surface-exposed lipoproteins and transmembrane outer membrane proteins were identified as candidates for development of vaccines for the prevention of leptospirosis.

Animals↗

The contribution of 700,000 ORF sequence tags to the definition of the human transcriptome.

Open reading frame expressed sequences tags (ORESTES) differ from conventional ESTs by providing sequence data from the central protein coding portion of transcripts. We generated a total of 696,745 ORESTES sequences from 24 human tissues and used a subset of the data that correspond to a set of 15,095 full-length mRNAs as a means of assessing the efficiency of the strategy and its potential contribution to the definition of the human transcriptome. We estimate that ORESTES sampled over 80% of all highly and moderately expressed, and between 40% and 50% of rarely expressed, human genes. In our most thoroughly sequenced tissue, the breast, the 130,000 ORESTES generated are derived from transcripts from an estimated 70% of all genes expressed in that tissue, with an equally efficient representation of both highly and poorly expressed genes. In this respect, we find that the capacity of the ORESTES strategy both for gene discovery and shotgun transcript sequence generation significantly exceeds that of conventional ESTs. The distribution of ORESTES is such that many human transcripts are now represented by a scaffold of partial sequences distributed along the length of each gene product. The experimental joining of the scaffold components, by reverse transcription-PCR, represents a direct route to transcript finishing that may represent a useful alternative to full-length cDNA cloning.

Expressed Sequence Tags↗

A new opto-mechanical effect in solids.

We propose that large, reversible shape changes in solids, of between 10%-400%, can be induced optically by photoisomerizing monodomain nematic elastomers. Empirical and molecular analysis of shape change and its relation to thermal effects is given along with a simple model of the dynamics of response. Our experiments demonstrate these effects for the first time and theory is compared qualitatively with our results.

Journal Article↗

Cylindrical phase of block copolymers: stability of circular configuration to elliptical distortions and thin film morphologies.

We study the cylindrical phase of a diblock copolymer melt in the strong segregation limit, and initially examine the stability of this morphology against elliptical perturbations. Surprisingly, we find that an elliptical conformation of the columns has lower free energy than a circular one. The size of the ellipse's eccentricity depends on f, the minority block fraction. We proceed to examine the morphology of the melt when placed between two hard, flat surfaces. The columns can either form with their axes in the plane of the bounding surfaces (denoted parallel) or with their axes perpendicular to the bounding surfaces. We determine when the parallel alignment is preferred over the perpendicular alignment.

Journal Article↗

Toroidal condensates of semiflexible polymers in poor solvents: adsorption, stretching, and compression.

When a semiflexible polymer chain is placed in a poor solvent, or in the presence of condensing agents, a toroidal condensate can result. In typical experiments, these condensates are adsorbed to surfaces. Here we examine the changes that can occur when a toroid is adsorbed. We then examine the behavior of a toroid when stretched and identify two regimes: a weak stretching regime where the toroid deforms from a circle to an ellipse, and a strong stretching regime where a tether is pulled from the toroid. In the weak stretching regime, the force increases linearly with separation whereas in the strong stretching regime, the applied force is a constant. We then look at the case of a toroid compressed in the plane of the toroid. In this case the form of the force law depends on how strongly the toroid wets the surfaces. In general, an inverse square force law is found.

Biophysical Phenomena↗

Identification of human chromosome 22 transcribed sequences with ORF expressed sequence tags.

Transcribed sequences in the human genome can be identified with confidence only by alignment with sequences derived from cDNAs synthesized from naturally occurring mRNAs. We constructed a set of 250,000 cDNAs that represent partial expressed gene sequences and that are biased toward the central coding regions of the resulting transcripts. They are termed ORF expressed sequence tags (ORESTES). The 250,000 ORESTES were assembled into 81,429 contigs. Of these, 1, 181 (1.45%) were found to match sequences in chromosome 22 with at least one ORESTES contig for 162 (65.6%) of the 247 known genes, for 67 (44.6%) of the 150 related genes, and for 45 of the 148 (30.4%) EST-predicted genes on this chromosome. Using a set of stringent criteria to validate our sequences, we identified a further 219 previously unannotated transcribed sequences on chromosome 22. Of these, 171 were in fact also defined by EST or full length cDNA sequences available in GenBank but not utilized in the initial annotation of the first human chromosome sequence. Thus despite representing less than 15% of all expressed human sequences in the public databases at the time of the present analysis, ORESTES sequences defined 48 transcribed sequences on chromosome 22 not defined by other sequences. All of the transcribed sequences defined by ORESTES coincided with DNA regions predicted as encoding exons by genscan. (http://genes.mit.edu/GENSCAN.html).

Chromosomes, Human, Pair 22↗

Thin diblock copolymer films on patterned surfaces: computer simulations and the Frenkel-Kontorowa model.

We study by direct numerical integration of the dynamical evolution equation the equilibrium configuration of a diblock copolymer thin film melt on a patterned surface. The surface has a large number of stripes and the mismatch between the bulk diblock spacing and the stripe width is small. We investigate primarily the formation of small discommensurations in the incommensurate phase and compare the results with the predictions of an analogous model of solid-state physics, the Frenkel-Kontorowa model.

Journal Article↗

A region of the cellobiohydrolase I promoter from the filamentous fungus Trichoderma reesei mediates glucose repression in Saccharomyces cerevisiae, dependent on mitochondrial activity.

The upstream activating region that controls cellulose-induced expression of the glucose-repressible cellobiohydrolase I gene (UARcb1) of the filamentous fungus Trichoderma reesei is shown to mediate transcription and glucose repression of a reporter gene in Saccharomyces cerevisiae, a unicellular microorganism that lacks the genes required for the utilization of cellulose. Glucose-controlled transcription mediated by UARcb1 requires the products of the genes SNF1 and SSN6, a protein kinase and a repressor, respectively, that regulate glucose-repressible yeast genes. Previously, it has been shown that mitochondrial function is implicated in cellobiohydrolase I gene expression in T. reesei and this sensitivity to the metabolic state of the mitochondria was shown to be transcriptionally controlled by the 5'-flanking sequence of the cbh1 gene [Abrahão-Neto et al. (1995) Biochemistry 34, 10456-10462]. Remarkably, transcription of the reporter gene controlled by UARcb1 in S. cerevisiae also showed a requirement for active mitochondria, suggesting that a common mechanism involving mitochondrial activity controls glucose-repressible genes in both microorganisms.

5' Untranslated Regions↗

Conserved regulation of the Hansenula polymorpha MOX promoter in Saccharomyces cerevisiae reveals insights in the transcriptional activation by Adr1p.

The Hansenula polymorpha MOX gene encodes a peroxisomal enzyme that catalyzes the first step of the highly specialized methanol metabolism. MOX is strongly transcribed in cells growing in methanol and completely repressed in glucose. We show here that the MOX promoter confers a glucose-repressible expression upon a lacZ reporter gene in Saccharomyces cerevisiae, an unrelated yeast species that lacks the methanol metabolism. Repression was mediated by a 200-bp region of the MOX promoter, termed MOX-B, and was counteracted by Adr1p, a transcription factor involved in the derepression of S. cerevisiae genes encoding peroxisomal proteins, the class to which MOX belongs. Binding of Adr1p to MOX-B was demonstrated by gel retardation and DNaseI-footprinting, and Adr1p was shown to interact with a DNA region containing only a half of the putative Adr1p consensus binding site. Our findings suggest that Adr1p is a conserved regulator for genes encoding peroxisomal proteins at least in other yeast species, and that its interaction with the DNA is dependent on the promoter context.

Alcohol Oxidoreductases↗

Transcriptional control of the cellulase genes in Trichoderma reesei.

The expression of the cellulase transcripts of Trichoderma reesei is controlled by the nature of the energy carbon sources used in the culture medium. Cellulose and the soluble disaccharide sophorose, but not glycerol or glucose, act as inducers. Evidence is presented suggesting that a low constitutive extracellular cellulolytic system catalyzes the formation of a soluble inducer from cellulose, and this inducer triggers the expression of the cellulase transcripts. This basal and cellulose-induced expression of the cellobiohydrolase I mRNAs (cbh1), the major member of the cellulase system, is transcriptionally controlled by two independent cis-acting DNA regions. In addition, expression of the cbh1 transcript is influenced by the physiological state of the mitochondria and this sensitivity is controlled through the 5'-flanking DNA sequence of this gene.

Cellulase↗