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PubMed2006

[Revista de Saúde Pública: forty years of Brazilian scientific production].

OBJECTIVE: To recognize the characteristics and path taken by the through analysis of the scientific production it has published over the period from 1967 to 2005. METHODS: Scientometric methods were used to analyze reference data on the articles published in the Revista, retrieved from the databases ISI/Thomson Scientific (Web of Science), National Library of Medicine (PubMed) and Scientific Electronic Library Online (SciELO). RESULTS: The Revista is the only Brazilian publication in the field of public health that is indexed by ISI/Thomson Scientific. It is prominent as a medium for publishing Brazilian scientific production in public health and is displaying a geometric increase in publication and citation, with annual rates of 4.4% and 12.7%, respectively. The mean number of authors per paper has risen from 2 to 3.5 over recent years. Although original research articles predominate, the numbers of reviews, multicenter studies, clinical trials and validation studies have been increasing. The number of articles published in foreign languages has also increased, accounting for 13% of the total, and the leading countries originating these are the UK, USA, Argentina and Mexico. The number and diversity of journals citing the Journal has been increasing, many of which are non-Brazilian. Authorship per author shows good fit to Lotka's Law, but the parameters suggest greater concentration and less dispersion than would be expected. Among the fields of interest of published papers, the following topics account for more than 50% of the total volume: infectious-parasitic diseases and vectors; health promotion, policies and administration; and epidemiology, surveillance and disease control. CONCLUSIONS: The Revista shows great dynamism, without signs of abating or reaching a plateau any time soon. There are signs of progressively increasing complexity in the studies published, and more multidisciplinary work. The Revista seems to be widening its outreach and recognition, while remaining faithful to the field of public health in Brazil.

Abstracting and Indexing↗
PubMed2006

Analysis of conserved hydrophobic cores in proteins and supramolecular complexes.

The conserved hydrophobic core is an important feature of a family of protein domains. We suggest a procedure for finding and the analysis of conserved hydrophobic cores. The procedure is based on using an original program called CluD (http://monkey.belozersky.msu.ru/CluD/cgi-bin/hftri.pl). Conserved hydrophobic cores of several families including homeodomains and interlock-containing domains are described. Hydrophobic clusters on some protein-DNA and protein-protein interfaces were also analyzed.

Binding Sites↗
PubMed1994

Visual response properties of single neurons in the temporal pole of behaving monkeys.

1. The responses of single neurons in the anterior part of the temporal cortex in monkeys, mainly the temporopolar cortex, area 36, and the most anterior part of area TE of von Bonin and Bailey (1947) (these areas were designated here as the temporal pole), were examined during the performance of a visual recognition memory task. The visual stimulus (sample stimulus) was presented when the monkey pressed a lever. The same sample stimulus was presented one to four times and, thereafter, a new stimulus was presented. The monkeys were trained to discriminate the new stimulus from the sample stimulus and to release the lever in response to the new stimulus. We used colored photographs of natural objects (human faces, monkeys, foods, and non-food objects) as complex visual stimuli or computer-generated two-dimensional shapes (a red square, a green circle, etc.) as simple visual stimuli. 2. In total, the activity of 311 neurons was recorded, and 225 of these responded to at least one visual stimulus. All visually responsive neurons were located in the ventral part of the temporal pole including the banks of the superior temporal sulcus. 3. The relationship between the monkey's eye movements and visual responses was investigated. Visual response properties, such as the number of spikes, onset latency, and response duration, were stable regardless of the monkey's eye positions and movements if the eyes were directed to the display. We also examined the receptive field property of neurons (n = 3). The neurons tested in the temporal pole tended to have a large receptive field (24 x 24 degrees). 4. The neurons tended to respond to different stimuli in different magnitudes. In each case, the maximal responses were elicited by complex, colored photographs, whereas simple, two-dimensional colored shapes elicited little or no responses. In 21% of the cases (47/225), the magnitude of the maximal response was significantly larger than for any of the other responses. 5. An achromatic version of the stimulus that induced the maximal response was tested in 53 neurons. About 80% of the neurons (41/53) responded to the achromatic stimulus at a magnitude that was not significantly different from the response to the original stimulus. In 12 neurons, the removal of color did significantly decrease the magnitude of the response. When other colors were tested, 3 of 9 neurons were found to code for color. 6. In 21 of these 53 neurons, a portion (the left-, right-, upper-, or lower-half) of the stimulus was also tested.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Co-operative interactions between NFI and the adenovirus DNA binding protein at the adenovirus origin of replication.

The DNA-protein and protein-protein interactions proposed for the stability of nucleoprotein complexes at the origin of replication in prokaryotes are also thought to impart regulatory precision in eukaryotic DNA replication. This type of specificity can be observed, for example, during adenovirus DNA replication where efficient initiation requires that nuclear factor I (NFI) binds to the origin of DNA replication. Addition of purified NFI stimulates the initiation of adenovirus DNA replication in vitro in a reaction that is dependent on the concentration of the adenovirus DNA binding protein (DBP). However, the molecular basis for the synergistic action of NFI and DBP during replication is at present unknown. We report here that DBP increases the affinity of NFI for its binding site in the replication origin. DBP did not, however, increase the affinity of another eukaryotic sequence-specific DNA binding protein, EBP1, for its recognition site. Other single-stranded DNA binding proteins could not substitute for DBP in increasing NFI affinity for its binding site. In addition, DBP was found to alter the binding kinetics of NFI, both by increasing the rate of association and decreasing the rate of dissociation of NFI with the DNA template. The co-operativity between NFI and DBP was also demonstrated on another DNA template, a human NFI site (FIB2), suggesting that this interaction is of general occurrence and not restricted to the adenovirus origin of replication.

Adenoviridae↗
PubMed2004

Saturation transfer difference NMR and computational modeling of a sialoadhesin-sialyl lactose complex.

The siglecs are a family of I-type lectins binding to sialic acids on the cell surface. Sialoadhesin (siglec-1) is expressed at much higher levels in inflammatory macrophages and specifically binds to alpha-2,3-sialylated N-acetyl lactosamine residues of glycan chains. The terminal disaccharide alpha-D-Neu5Ac-(2-->3)-beta-D-Gal is thought to be the main epitope recognized by sialoadhesin. To understand the basis of this biological recognition reaction we combined NMR experiments with a molecular modeling study. We employed saturation transfer difference (STD) NMR experiments to characterize the binding epitope of alpha-2,3-sialylated lactose, alpha-D-Neu5Ac-(2-->3)-beta-D-Gal-(1-->4)-D-Glc 1 to sialoadhesin at atomic resolution. The experimental results were compared to a computational docking model and to X-ray data of a complex of sialyl lactose and sialoadhesin. The data reveal that sialoadhesin mainly recognizes the N-acetyl neuraminic acid and a small part of the galactose moiety of 1. The crystal structure of a complex of sialoadhesin with sialyl lactose 1 was used as a basis for a modeling study using the FlexiDock algorithm. The model generated was very similar to the original crystal structure. Therefore, the X-ray data were used to predict theoretical STD values utilizing the CORCEMA-STD protocol. The good agreement between experimental and theoretical STD values indicates that a combined modeling/STD NMR approach yields a reliable structural model for the complex of sialoadhesin with alpha-D-Neu5Ac-(2-->3)-beta-D-Gal-(1-->4)-D-Glc 1 in aqueous solution.

Carbohydrate Sequence↗
PubMed1994

Enzyme inhibitory autoantibodies to pyruvate dehydrogenase complex in primary biliary cirrhosis differ for mammalian, yeast and bacterial enzymes: implications for molecular mimicry.

Primary biliary cirrhosis is a chronic autoimmune disease in which serum autoantibodies against the mitochondrial 2-oxo acid dehydrogenase enzyme complexes (M2 antibodies) are regularly present. Molecular mimicry of host proteins by bacterial counterparts is a suggested explanation for the origin of these autoantibodies. We tested this hypothesis by measuring the functional reactivity of serum autoantibodies by means of an enzyme inhibition assay against pyruvate dehydrogenase complex from different sources: mammalian, Saccharomyces cerevisiae and Escherichia coli. The 10 primary biliary cirrhosis sera all reacted on immunofluorescence study for M2 antibodies and on immunoblotting with the pyruvate dehydrogenase complex E2 subunit from each of the three enzymes, but there were strikingly different inhibitory capacities. The primary biliary cirrhosis sera were highly inhibitory for mammalian pyruvate dehydrogenase complex (10 of 10 inhibitory; mean level of inhibition, 99%), moderately inhibitory for yeast pyruvate dehydrogenase complex (10 of 10 inhibitory; mean level, 70%) and weakly inhibitory for Escherichia coli pyruvate dehydrogenase complex (4 of 10 inhibitory; mean level, 26%). Thus, with a functional assay that depends on epitope recognition of primary biliary cirrhosis sera, cross-reactivity between mammalian and bacterial pyruvate dehydrogenase complex enzymes is low and molecular mimicry, at least at the B-lymphocyte level, is not supported.

Animals↗
PubMed2000

An alternative approach to deal with geometric uncertainties in computer analysis of two-dimensional electrophoresis gels.

With the growing importance of proteomics in biomedical and pharmaceutical sciences a need has emerged for computing tools that are capable of digitally visualizing and analyzing protein spot patterns within two-dimensional electrophoresis (2-DE) gel. Matching programs need to meet requirements such as interlaboratory comparison and the comparison of samples from different origins. For such research purposes, we have developed the CAROL system that implements new algorithms for spot detection and matching, which enable researchers to take a different approach to protein spot identification and comparison. The present short communication discusses how the system deals with uncertain geometric spot information that arises from streaks and complex spot regions and how this can be amplified for the matching procedure.

Algorithms↗
PubMed2001

DNA amplification associated with double minutes originating from chromosome 19 in mouse hepatocellular carcinoma.

DNA amplification is associated with genomic instability, the main characteristic of cancer cells, and it frequently involves protooncogenes. Double minute chromosomes (DM) and homogeneously stained regions (HSR) are cytological manifestations of DNA amplification. Gain of chromosome 19 is a recurrent alteration in mouse hepatocellular carcinoma (HCC). In one tumor cell line established from HCC developed in myc transgenic mice, DM derived from chromosome 19 were identified by spectral karyotyping and confirmed by fluorescence in situ hybridization (FISH). A probe generated by PCR from microdissected DM was localized by FISH on normal and HCC-derived cell lines on DM and chromosome 19 at two sites separated by several medium size G-bands. This organization of DM containing amplified sequences from separate loci of the same chromosome, indicates a complex mechanism of DNA amplification, possibly involving more than one gene. DM or HSR were not previously identified in mouse HCC and adult human HCC. The recognition of these loci could lead to the cloning of new genes or identification of known genes important in development or progression of HCC.

Animals↗
PubMed2006

AffinDB: a freely accessible database of affinities for protein-ligand complexes from the PDB.

AffinDB is a database of affinity data for structurally resolved protein-ligand complexes from the Protein Data Bank (PDB). It is freely accessible at http://www.agklebe.de/affinity. Affinity data are collected from the scientific literature, both from primary sources describing the original experimental work of affinity determination and from secondary references which report affinity values determined by others. AffinDB currently contains over 730 affinity entries covering more than 450 different protein-ligand complexes. Besides the affinity value, PDB summary information and additional data are provided, including the experimental conditions of the affinity measurement (if available in the corresponding reference); 2D drawing, SMILES code and molecular weight of the ligand; links to other databases, and bibliographic information. AffinDB can be queried by PDB code or by any combination of affinity range, temperature and pH value of the measurement, ligand molecular weight, and publication data (author, journal and year). Search results can be saved as tabular reports in text files. The database is supposed to be a valuable resource for researchers interested in biomolecular recognition and the development of tools for correlating structural data with affinities, as needed, for example, in structure-based drug design.

Databases, Protein↗
PubMed1993

Members of the ALDH gene family are lens and corneal crystallins.

Many of the major lens proteins, known as crystallins, responsible for the structural integrity and functional utility of this visual tissue have been previously shown to be recruited proteins. This phenomena of a protein that is expressed and functions elsewhere acquiring a new function in another tissue has been termed 'gene sharing'. It is now becoming obvious that the cornea of vertebrates has similarly acquired proteins, and that at least one corneal protein, ALDH3 belongs to a gene family that has been previously identified as a lens crystallin. The recognition that both lens and corneal crystallins exist is a novel concept that has implications that involve the process by which multifunctional gene products have evolved. Members of the ALDH gene family function in both the cornea and lens as crystallins and the acquisition of multifunctionality by this gene family is unique. Based on our analysis we have deduced a supragene family relationship between the thiol protein esterases, aldehyde dehydrogenases, and the taxon-specific crystallins. Evolution of a complex organ such as the vertebrate eye is not a sequential and gradual process such as the Darwinian Giraffe's neck, since the eye can provide selective advantage only as a complete organ. Catastrophic theory proposes that the complex vertebrate eye with its lens, and focussing mechanism arose from the primitive eye spot which contained originally only the photoreceptor system by a one step event. In the evolution of the vertebrate eye it is evolutionarily plausible that several pre-existing proteins have been recruited to perform a structural role for this complex organ. It is also incumbent in evolutionary thought that any inherent enzymatic activity associated with this protein would be purely an incidental addition to the organ. However, the fact that most of these have pyridine nucleotide binding capacity, which is presumed important in giving protection from UV exposure, is noteworthy. Finally, to construct the vertebrate eye in one step from the existing visual pigment system such as the eyespot of unicellular organisms the following criteria would apparently be advantageous: (1) high water solubility; (2) transparency; and (3) common genetic regulatory elements (e.g. promoters/enhancers). Although it is an important observation that certain members of the aldehyde dehydrogenase gene family are present as structural proteins in the cornea and lens, it is not surprising that the phenomenon of gene sharing extends to another ocular tissue such as the cornea. In this context, it will be interesting to note if similar multifunctional gene products will be found as frequently in organs other than the eye.

Aldehyde Dehydrogenase↗
PubMed2005

The moving parts of the nucleolus.

The cell nucleolus is the subnuclear body in which ribosomal subunits are assembled, and it is also the location of several processes not related to ribosome biogenesis. Recent studies have revealed that nucleolar components move about in a variety of ways. One class of movement is associated with ribosome assembly, which is a vectorial process originating at the sites of transcription in the border region between the fibrillar center and the dense fibrillar component. The nascent preribosomal particles move outwardly to become the granular components where further maturation takes place. These particles continue their travel through the nucleoplasm for eventual export to the cytoplasm to become functional ribosomes. In a second kind of motion, many nucleolar components rapidly exchange with the nucleoplasm. Thirdly, nucleolar components engage in very complex movements when the nucleolus disassembles at the beginning of mitosis and then reassembles at the end of mitosis. Finally, many other cellular and viral macromolecules, which are not related to ribosome assembly, also pass through or are retained by the nucleolus. These are involved in nontraditional roles of the nucleolus, including regulation of tumor suppressor and oncogene activities, signal recognition particle assembly, modification of small RNAs, control of aging, and modulating telomerase function.

Animals↗
PubMed2006

Polarimetric image segmentation via maximum-likelihood approximation and efficient multiphase level-sets.

This study investigates a level set method for complex polarimetric image segmentation. It consists of minimizing a functional containing an original observation term derived from maximum-likelihood approximation and a complex Wishart/Gaussian image representation and a classical boundary length prior. The minimization is carried out efficiently by a new multiphase method which embeds a simple partition constraint directly in curve evolution to guarantee a partition of the image domain from an arbitrary initial partition. Results are shown on both synthetic and real images. Quantitative performance evaluation and comparisons are also given.

Algorithms↗
PubMed2006

Dendritic cells at the oral mucosal interface.

The mucosal lining of the respiratory and digestive systems contains the largest and most complex immune system in the body, but surprisingly little is known of the immune system that serves the oral mucosa. This review focuses on dendritic cells, particularly powerful arbiters of immunity, in response to antigens of microbial or tumor origin, but also of tolerance to self-antigens and commensal microbes. Although first discovered in 1868, the epidermal dendritic Langerhans cells remained enigmatic for over a century, until they were identified as the most peripheral outpost of the immune system. Investigators' ability to isolate, enrich, and culture dendritic cells has led to an explosion in the field. Presented herein is a review of dendritic cell history, ontogeny, function, and phenotype, and the role of different dendritic cell subsets in the oral mucosa and its diseases. Particular emphasis is placed on the mechanisms of recognition and capture of microbes by dendritic cells. Also emphasized is how dendritic cells may regulate immunity/tolerance in response to oral microbes.

Animals↗
PubMed1985

Ultrastructural analysis of central serotoninergic neurons immunolabeled by silver-gold-intensified diaminobenzidine chromogen. Completion of immunocytochemistry with X-ray microanalysis.

Serotonin immunoreactive structures of the rat central nervous system (CNS) were detected by the recently developed silver-intensified peroxidase-antiperoxidase complex (SI-PAP) method at both the light and electron microscopic levels. The silver postintensification of the diaminobenzidine (DAB) chromogen increased the sensitivity of the original PAP method, resulting in a very Golgi-like appearance of serotonin-immunopositive neuronal elements. The metallic silver and gold deposited onto DAB-labeled organelles, filling out the whole immunoreactive neuron, assures the easy tracing of thin neuronal processes far from the cell body. At the ultrastructural level, metallic grains were seen over immunolabeled structures only, proving the specificity of the silver method. In neurons of the dorsal raphe nucleus, free ribosomes, endoplasmic reticulum, and granules (80-100 nm in diameter) were labeled. Immunoreactive, e.g., serotoninergic, dendrites were seen to receive afferent terminals. The increased electron density of the intensified immunolabel facilitates the ultrastructural recognition of even weakly labeled profiles, while its metallic components (Ag and Au) provide a base for X-ray analysis of the immunolabeled biological specimen.

3,3'-Diaminobenzidine↗
PubMed2000

MSSP promotes ras/myc cooperative cell transforming activity by binding to c-Myc.

BACKGROUND: MSSPs, myc single strand binding proteins, were originally identified as proteins recognizing a putative replication origin/transcriptional enhancer in the human c-Myc gene. The cDNAs encoding four of the family proteins, MSSP-1, MSSP-2, Scr2 and Scr3, were cloned. These proteins carry two copies of the putative RNA binding domains, RNP-A and RNP-B, and have been suggested to participate in DNA replication and cell cycle progression from the G1 to the S phase. RESULTS: We report that MSSP-1 and MSSP-2 bound directly to the C-terminal portion of c-Myc, along with Max, side by side. MSSP, c-Myc and Max formed a ternary complex in vivo, although MSSP did not directly associate with Max. The MSSP/Myc/Max ternary complex lost the binding activity to the E-box sequence-the recognition sequence of c-Myc/Max complex-thereby abrogating the E-box-dependent transcription activity of c-Myc. MSSP specifically stimulated the cooperative transforming activity of c-myc with ras, in a manner dependent upon the RNP sequences, while mssp itself showed no transforming activity in mouse NIH3T3 cells. The NIH3T3 transformants, together with ras, myc and mssp, grew to form very large colonies in soft agar, as compared to those with ras plus myc or ras alone. CONCLUSIONS: MSSP is a modulator of c-Myc and the c-Myc/MSSP complex may deregulate cell cycle controls and lead cells towards transforming pathways.

3T3 Cells↗
PubMed2007

Male mating preferences pre-date the origin of a female trait polymorphism in an incipient species complex of Lake Victoria cichlids.

Disruptive sexual selection on colour patterns has been suggested as a major cause of diversification in the cichlid species flock of Lake Victoria. In Neochromis omnicaeruleus, a colour and sex determination polymorphism is associated with a polymorphism in male and female mating preferences. Theoretical work on this incipient species complex found conditions for rapid sympatric speciation by selection on sex determination and sexual selection on male and female colour patterns, under restrictive assumptions. Here we test the biological plausibility of a key assumption of such models, namely, the existence of a male preference against a novel female colour morph before its appearance in the population. We show that most males in a population that lacks the colour polymorphism exhibit a strong mating preference against the novel female colour morph and that reinforcement is not a likely explanation for the origin of such male preferences. Our results show that a specific condition required for the combined action of selection on sex determination and sexual selection to drive sympatric speciation is biologically justified. Finally, we suggest that Lake Victoria cichlids might share an ancestral female recognition scheme, predisposing colour monomorphic populations/species to similar evolutionary pathways leading to divergence of colour morphs in sympatry.

Animals↗
PubMed1990

Temporal encoding of two-dimensional patterns by single units in primate primary visual cortex. I. Stimulus-response relations.

1. Previously we developed a new approach for investigating visual system neuronal activity in which single neurons are considered to be communication channels transmitting stimulus-dependent codes in their responses. Application of this approach to the stimulus-response relations of inferior temporal (IT) neurons showed that these carry stimulus-dependent information in the temporal modulation as well as in the strength of their responses. IT cortex is a late station in the visual processing stream. Presumably the neuronal properties arise from the properties of the inputs. However, the discovery that IT neuronal spike trains transmit information in stimulus-dependent temporally modulated codes could not be assumed to be true for those earlier stations, so the techniques used in the earlier study were applied to single-striate cortical neurons in the studies reported here. 2. Single-striate cortical neurons were recorded from three awake, fixating rhesus monkeys. The neurons were stimulated by two sets of patterns. The first set was made up of 128 black-and-white patterns based on a complete, orthogonal set of two-dimensional Walsh-Hadamard functions. These stimuli appear as combinations of black-and-white rectangles and squares, and they fully span the range of all possible black-and-white pictures that can be constructed in an 8 x 8 grid. Except for the stimulus that appeared as an all-white or all-black square, each stimulus had equal areas of white and black. The second stimulus set was made up of single bars constructed in the same 8 x 8 grid as the Walsh stimuli. These were presented both as black against a gray background and white against a gray background. The stimuli were centered on the receptive field, and each member of the stimulus set was presented once before any stimulus appeared again. 3. The responses of 21 striate cortical neurons were recorded and analyzed. Two were identified as simple cells and the other 19 as complex cells according to the criteria originally used by Hubel and Wiesel. The stimulus set elicited a wide variety of response strengths and patterns from each neuron. The responses from both the bars and the Walsh set could be used to differentiate and classify simple and complex cells. 4. The responses of both simple and complex cells showed striking stimulus-related strength and temporal modulation. For all of the complex cells there were instances where the responses to a stimulus and its contrast-reversed mate were substantially different in response strength or pattern, or both.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

Myasthenia gravis and myasthenic syndromes.

More than a decade ago myasthenic symptoms were observed in rabbits immunized with acetylcholine receptor (AChR) [119] and AChR deficiency was found at the neuromuscular junction in human myasthenia gravis (MG) [36]. By 1977 the autoimmune character of MG and the pathogenic role of AChR antibodies had been established by several measures. These included the demonstration of circulating AChR antibodies in nearly 90% of patients with MG [87], passive transfer with IgG of several features of the disease from human to mouse [149], localization of immune complexes (IgG and complement) on the postsynaptic membrane [30], and the beneficial effects of plasmapheresis [20, 123]. Substantial subsequent progress has occurred in understanding the structure and function of AChR and its interaction with AChR antibodies. The relationships of the concentration, specificities, and functional properties of the antibodies to the clinical state in MG have been carefully analyzed, and the mechanisms by which AChR antibodies impair neuromuscular transmission have been further investigated. The clinical classification of MG has been refined, the role of the thymus gland in the disease has been further clarified, and new information has become available on transient neonatal MG. The prognosis for generalized MG is improving, but there is still no consensus on its optimal management. Novel therapeutic approaches to MG are now being explored in animal models. Recognition of the autoimmune origin of acquired MG also implied that myasthenic disorders occurring in a genetic or congenital setting had a different cause. As a result, a number of congenital myasthenic syndromes have come to be recognized and investigated. Finally, an acquired disorder of neuromuscular transmission different from MG, the Lambert-Eaton myasthenic syndrome, has also been shown to have an autoimmune basis. In this syndrome, active zone particles of the presynaptic membrane are direct or indirect targets of the pathogenic autoantibodies.

Acetylcholinesterase↗