PubMed Health⌕ Search

Biomedical subjects

E Rivas

Publications and source records attributed to E Rivas.

At least 19 recordsLinked to original sources

Computational identification of noncoding RNAs in E. coli by comparative genomics.

Some genes produce noncoding transcripts that function directly as structural, regulatory, or even catalytic RNAs [1, 2]. Unlike protein-coding genes, which can be detected as open reading frames with distinctive statistical biases, noncoding RNA (ncRNA) gene sequences have no obvious inherent statistical biases [3]. Thus, genome sequence analyses reveal novel protein-coding genes, but any novel ncRNA genes remain invisible. Here, we describe a computational comparative genomic screen for ncRNA genes. The key idea is to distinguish conserved RNA secondary structures from a background of other conserved sequences using probabilistic models of expected mutational patterns in pairwise sequence alignments. We report the first whole-genome screen for ncRNA genes done with this method, in which we applied it to the "intergenic" spacers of Escherichia coli using comparative sequence data from four related bacteria. Starting from >23,000 conserved interspecies pairwise alignments, the screen predicted 275 candidate structural RNA loci. A sample of 49 candidate loci was assayed experimentally. At least 11 loci expressed small, apparently noncoding RNA transcripts of unknown function. Our computational approach may be used to discover structural ncRNA genes in any genome for which appropriate comparative genome sequence data are available.

Animals↗

Synthesis and biological studies of glycosyl dopamine derivatives as potential antiparkinsonian agents.

A new approach to deliver dopamine into the central nervous system, based on the use of D-glucose as transportable agent, has been studied. Glycosyl dopamine derivatives bearing the sugar moiety linked to either the amino group or the catechol ring of dopamine through amide, ester or glycosidic bonds were synthesised as potential antiparkinsonian agents. Studies on the binding to dopamine D2 receptor, in vitro stability, and locomotive effect in mice of the synthetic glycoconjugates are reported.

Animals↗

Biochemical and biophysical studies of Bacillus subtilis envelopes under hyperosmotic stress.

The behaviour and state of the envelopes from B. subtilis cultures grown in Luria Bertani (LB) medium with and without 1.5 M NaCl are compared. Under hypertonic conditions, the hydrophobicity of the cultures increases. The phospholipid and fatty acid (FA) compositions show important differences: a higher cardiolipin (CL) content [at the expense of phosphatidylglycerol (PG)], and a higher unsaturated and straight chain FA content. The fluidity of the membranes, determined with fluorescent probes, indicates an increase in viscosity of the cytoplasmic membrane. The consequences of these variations in membrane permeability and osmotolerance are discussed.

Bacillus subtilis↗

[Invagination of the ileum as the etiology of acute abdomen in adults].

In contrast to children, intussusception is an unusual cause of an abdominal emergency in adults. We report on a 65-year-old patient who complained of inconstant crampy abdominal pain for a period of over 6 months. He was admitted to our hospital because of acute intestinal obstruction. Sonography and computer tomography suggested an intussusception. At surgery the diagnosis of an ileo-ileal invagination was confirmed and resection of a segment of the ileum was performed. As shown by macroscopic findings intussusception had existed for several days. Histologically, the underlying disease causing the intussusception was a leiomyoma arising from the submucosa.

Abdomen, Acute↗

The language of RNA: a formal grammar that includes pseudoknots.

MOTIVATION: In a previous paper, we presented a polynomial time dynamic programming algorithm for predicting optimal RNA secondary structure including pseudoknots. However, a formal grammatical representation for RNA secondary structure with pseudoknots was still lacking. RESULTS: Here we show a one-to-one correspondence between that algorithm and a formal transformational grammar. This grammar class encompasses the context-free grammars and goes beyond to generate pseudoknotted structures. The pseudoknot grammar avoids the use of general context-sensitive rules by introducing a small number of auxiliary symbols used to reorder the strings generated by an otherwise context-free grammar. This formal representation of the residue correlations in RNA structure is important because it means we can build full probabilistic models of RNA secondary structure, including pseudoknots, and use them to optimally parse sequences in polynomial time.

Algorithms↗

Secondary structure alone is generally not statistically significant for the detection of noncoding RNAs.

MOTIVATION: Several results in the literature suggest that biologically interesting RNAs have secondary structures that are more stable than expected by chance. Based on these observations, we developed a scanning algorithm for detecting noncoding RNA genes in genome sequences, using a fully probabilistic version of the Zuker minimum-energy folding algorithm. RESULTS: Preliminary results were encouraging, but certain anomalies led us to do a carefully controlled investigation of this class of methods. Ultimately, our results argue that for the probabilistic model there is indeed a statistical effect, but it comes mostly from local base-composition bias and not from RNA secondary structure. For the thermodynamic implementation (which evaluates statistical significance by doing Monte Carlo shuffling in fixed-length sequence windows, thus eliminating the base-composition effect) the signals for noncoding RNAs are still usually indistinguishable from noise, especially when certain statistical artifacts resulting from local base-composition inhomogeneity are taken into account. We conclude that although a distinct, stable secondary structure is undoubtedly important in most noncoding RNAs, the stability of most noncoding RNA secondary structures is not sufficiently different from the predicted stability of a random sequence to be useful as a general genefinding approach.

Algorithms↗

A dynamic programming algorithm for RNA structure prediction including pseudoknots.

We describe a dynamic programming algorithm for predicting optimal RNA secondary structure, including pseudoknots. The algorithm has a worst case complexity of O(N6) in time and O(N4) in storage. The description of the algorithm is complex, which led us to adopt a useful graphical representation (Feynman diagrams) borrowed from quantum field theory. We present an implementation of the algorithm that generates the optimal minimum energy structure for a single RNA sequence, using standard RNA folding thermodynamic parameters augmented by a few parameters describing the thermodynamic stability of pseudoknots. We demonstrate the properties of the algorithm by using it to predict structures for several small pseudoknotted and non-pseudoknotted RNAs. Although the time and memory demands of the algorithm are steep, we believe this is the first algorithm to be able to fold optimal (minimum energy) pseudoknotted RNAs with the accepted RNA thermodynamic model.

Algorithms↗

In vivo effects of new inhibitors of catechol-O-methyl transferase.

1. The effects of two new synthetic compounds showing in vitro catechol-O-methyl transferase (COMT) inhibitor properties were studied in vivo and compared with the effects of nitecapone and Ro-41-0960. 2. QO IA (3-(3-hydroxy-4-methoxy-5-nitrobenzylidene)-2,4-pentanedione), QO IIR ([2-(3,4-dihydroxy-2-nitrophenyl)vinyl]phenyl ketone), nitecapone and Ro-41-0960 (30 mg kg(-1), i.p.) were given to reserpinized rats 1 h before the administration of L-DOPA/carbidopa (LD/CD, 50:50 mg kg(-1), i.p.). Locomotor activity was assessed 1 h later. All the COMT inhibitors (COMTI), with the exception of QO IA, markedly potentiated LD/CD reversal of reserpine-induced akinesia. Similar results were obtained when the COMTI were coadministered with LD/CD. The effect of compound QO IIR was dose-dependent (7.5-30 mg kg(-1), i.p.). 3. The COMTI (30 mg kg(-1), i.p.) potentiated LD/CD reversal of both catalepsy and hypothermia of reserpinized mice. 4. QO IIR, nitecapone and Ro-41-0960 (30 mg kg(-1), i.p.) reduced striatal 3-methyl-DOPA (3-OMD) levels and increased dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) levels. Compound QO IA was devoid of any effect on striatal amine levels. In contrast to the other inhibitors, Ro-41-0961 reduced HVA levels as well. The effect of QO IIR on striatal amine levels was dose-dependent (7.5-60 mg kg(-1), i.p.) 5. These results suggest that the new compound QO IIR is an effective peripherally acting COMT inhibitor in vivo.

Animals↗

Osmotic strength blocks sporulation at stage II by impeding activation of early sigma factors in Bacillus subtilis.

In Bacillus subtilis, osmotolerance is a stationary phase-dependent, adaptive response inhibiting sporulation and sharing common regulators with this process. The extent of this inhibition was determined by measuring transcription activity of promoter lacZ fusions to early sigma genes (spoIIG and spoIIA coding for precursors of sigmaE and sigmaF) and to reporters of them (spoIID, spoIIQ and spoIIIG), in the absence and presence of 0.6 M or 1 M NaCl. The transcription activity of these sigma precursors, normally occurring at the onset of the stationary phase, was reduced to 30-50% of their maximal expression in hyperosmotic conditions; expression of genes under their control was, however, more inhibited (<10%). Therefore, sporulation was blocked at the sigma sigmaE and sigmaF activation steps. This assumption was confirmed by electron microscopic examinations of hyperosmotic cultures, which presented asymmetric septa characteristic of stage II mutants. Discussion was focused on the particular composition and/or structure of membranes during hyperosmotic growth and their involvement in the arrest of sporulation.

Bacillus subtilis↗

Diacylglycerol and the promotion of lamellar-hexagonal and lamellar-isotropic phase transitions in lipids: implications for membrane fusion.

Changes in steady-state fluorescence anisotropy of 1 -(4-trimethylaminophenyl)-6-phenyl-1,3,5-hexatriene TMA-DPH) are applied to the detection of lamellar-hexagonal transitions in egg phosphatidylethanolamine. Even low (2 mole%) proportions of diacylglycerol decrease the hexagonal transition temperature considerably, as confirmed by differential scanning calorimetry. Diacylglycerol is also found to promote a lamellar to "isotropic" (Q(224) cubic) transition in mixtures of phosphatidylcholine: phosphatidylethanolamine:cholesterol. This nonreversible transition is also observed by (31)P nuclear magnetic resonance and detected as a large increase in TMA-DPH steady-state anisotropy. The same technique reveals as well that lysophosphatidylcholine counteracts the effect of diacylglycerol and stabilizes the lamellar phase in both transitions. Diacylglycerol and lysophosphatidylcholine are known to respectively promote and inhibit membrane fusion in a variety of systems. These data are interpreted in support of the hypothesis of a highly bent structural fusion intermediate ("stalk"). They also show the interest of lipid-phase studies in predicting and rationalizing membrane fusion mechanisms.

Calorimetry, Differential Scanning↗

[Gliomatosis cerebri. Ante-mortem diagnosis].

Gliomatosis Cerebri is an unusual neoplastic entity that affects the central nervous system (C.N.S.); it consists of a marked proliferation of glial cells with variable degrees of differentiation in extensive areas of the brain and/or spinal cord. The process is primarily an infiltrative one rather than destructive. Most of the cases are diagnosed at autopsy. The authors report a new case of Gliomatosis Cerebri in a 46 year old woman, with a long clinical history--15 years--of focal seizures; and during the year prior to her admission: behavioral changes, vertigo, urinary incontinence and frequent falls. C.N.S. imaging revealed extensive involvement of the white matter of both cerebral hemispheres. Stereotactic guided biopsy showed a moderately cellular astrocytic neoplasm. A review of the medical literature led to the conclusion that the present case constitutes one of the very few examples in which the diagnosis of Gliomatosis Cerebri was achieved ante-mortem.

Biopsy↗

[Resection with primary anastomosis in complicated diverticulitis. Risk analysis].

107 patients operated for complicated diverticulitis 1988 until 1993 were analysed retrospectively regarding perioperative risk of resection with primary anastomosis (n = 94). 53 of them had peridiverticulitis with stenosis (mortality 0), 41 had emergency operations (mortality 14.6%). Hartmann procedure (n = 13, mortality 7.6%) has been accepted only for the following situations: 1. ileus with secondary damage of the bowel, 2. extended diffuse peritonitis with secondary organ failure, 3. poor blood supply of the bowel, 4. the patient under immunosuppression after transplantation. Regarding these recommendations mortality rate in emergency operations (12.9%) has been lower as compared to 15 to 20% in literature. So regarding the recommendations named above resection with primary anastomosis seems to be a safe procedure in complicated diverticulitis.

Adult↗

A comparative study of azithromycin and amoxycillin in paediatric patients with acute otitis media.

In this open study, a three-day regimen of azithromycin (single daily dose of 10 mg/kg) was compared with a ten-day regimen of amoxycillin paediatric suspension (30 mg/kg/day in three divided doses; children > 20 kg received 250 mg tid daily) in 154 children (aged 2-12 years) with a clinical diagnosis of acute otitis media (13 recurrent). Full clinical, bacteriological and laboratory safety assessments were performed during and after the study. Of the 77 azithromycin patients, 61 (79%) were considered cured, 15 (19%) improved and one (1%) failed, compared with 45 (58%) cured, 28 (36%) improved and four (5%) failed among the 77 amoxycillin patients. Excluding from analysis the 13 patients with recurrent otitis media, azithromycin was found to be significantly superior to amoxycillin (P = 0.003). The incidence of side-effects was low, with only two (3%) and three (4%) patients reporting adverse events with azithromycin and amoxycillin, respectively. These were gastrointestinal in nature and of mild or moderate severity, except for one case of severe diarrhoea in the amoxycillin group. No treatment-related abnormalities in the laboratory safety tests were observed, and no patients withdrew from therapy. A three-day regimen of azithromycin was therefore shown to be more effective than, and as well tolerated as, amoxycillin in the treatment of children with acute otitis media.

Acute Disease↗

Partial dehydration of phosphatidylethanolamine phosphate groups during hexagonal phase formation, as seen by i.r. spectroscopy.

The gel-to-fluid and lamellar-to-HII-hexagonal thermotropic phase transitions of egg-yolk phosphatidylethanolamine have been examined by Fourier-transform infrared spectroscopy under a variety of conditions, namely excess water at pH 5.0, excess water at pH 9.5 and low hydration. The various lamellar and hexagonal phases have been characterized by X-ray diffraction. At pH 5.0, gel-fluid and lamellar-hexagonal transitions were detected at 10 and 32 degrees C respectively, in accordance with previous data. At pH 9.5, only the first of these two transitions was detected. In the partially hydrated sample a single phenomenon was observed, probably encompassing both transitions, so that, in practice, a gel-HII-hexagonal transition appears to occur. The region of the i.r. spectrum corresponding to the phospholipid phosphate group reveals that the lamellar-hexagonal, but not the gel-fluid, transition is accompanied by a weakening in the shell of hydrogen-bonded water, thus providing direct evidence that, in a pure lipid/water system, hexagonal phase formation requires partial dehydration of the phospholipid phosphate group. X-ray diffraction data support this conclusion, since, at least in the low-hydration system, the average surface area per lipid polar group decreases with the thermotropic lamellar-hexagonal transition.

Fourier Analysis↗

Lipid polymorphism: a correction. The structure of the cubic phase of extinction symbol Fd-- consists of two types of disjointed reverse micelles embedded in a three-dimensional hydrocarbon matrix.

The X-ray scattering study of a cubic phase of extinction symbol Fd--, recently performed on a lipid extract (PFL) from Pseudomonas fluorescens [Mariani et al. (1990) Biochemistry 29, 6799-6810] has been extended to several other systems, all consisting of mixtures of water-miscible (MO, PC, PE, oleate) and of water-immiscible (FA, DG) lipids, plus water. In all of these systems the cubic phase was observed in the presence of excess water. Some inconsistencies observed between PFL and the other systems, the fact that in PFL one of the reflections of the cubic phase happened to coincide with the strongest reflection of the hexagonal phase, and the finding, in one of the original cubic samples of PFL kept in the cold for more than 3 years, that the intensity of one of the reflections had decreased dramatically all indicated that a nonnegligible amount of a hexagonal impurity was in fact present in the samples of PFL originally thought to contain a pure cubic phase. The intensities were corrected for that impurity and analyzed again using a pattern recognition approach based upon the axiom that the histogram of the electron density maps is invariant with respect to physical structure, when different phases are compared whose chemical composition is the same. The hexagonal phase provided the reference phase for the comparison. The moments mean value of (delta rho)n were used to compare the histograms.(ABSTRACT TRUNCATED AT 250 WORDS)

Crystallography↗