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PubMed2006

Temporal coding mediates discrimination of "bitter" taste stimuli by an insect.

The mechanisms that mediate discriminative taste processing in insects are poorly understood. We asked whether temporal patterns of discharge from the peripheral taste system of an insect (Manduca sexta caterpillars; Sphingidae) contribute to the discrimination of three "bitter" taste stimuli: salicin, caffeine, and aristolochic acid. The gustatory response to these stimuli is mediated exclusively by three pairs of bitter-sensitive taste cell, which are located in the medial, lateral, and epipharyngeal sensilla. We tested for discrimination by habituating the caterpillars to salicin and then determining whether the habituation generalized to caffeine or aristolochic acid. We ran habituation-generalization tests in caterpillars with their full complement of taste sensilla (i.e., intact) and in caterpillars with ablated lateral sensilla (i.e., lat-ablated). The latter perturbation enabled us to examine discrimination in caterpillars with a modified peripheral taste profile. We found that the intact and lat-ablated caterpillars both generalized the salicin-habituation to caffeine but not aristolochic acid. Next, we determined whether this pattern of stimulus-generalization could be explained by salicin and aristolochic acid generating distinct ensemble, rate, temporal, or spatiotemporal codes. To this end, we recorded excitatory responses from the bitter-sensitive taste cells and then used these responses to formulate predictions about whether the salicin-habituation should generalize to caffeine or aristolochic acid, separately for each coding framework. We found that the pattern of stimulus generalization in both intact and lat-ablated caterpillars could only be predicted by temporal coding. We conclude that temporal codes from the periphery can mediate discriminative taste processing.

Animals↗
PubMed2005

Identification of coding and non-coding sequences using local Holder exponent formalism.

MOTIVATION: Accurate prediction of genes in genomes has always been a challenging task for bioinformaticians and computational biologists. The discovery of existence of distinct scaling relations in coding and non-coding sequences has led to new perspectives in the understanding of the DNA sequences. This has motivated us to exploit the differences in the local singularity distributions for characterization and classification of coding and non-coding sequences. RESULTS: The local singularity density distribution in the coding and non-coding sequences of four genomes was first estimated using the wavelet transform modulus maxima methodology. Support vector machines classifier was then trained with the extracted features. The trained classifier is able to provide an average test accuracy of 97.7%. The local singularity features in a DNA sequence can be exploited for successful identification of coding and non-coding sequences. CONTACT: Available on request from bd.kulkarni@ncl.res.in.

Algorithms↗
PubMed2002

Probabilistic prediction of Saccharomyces cerevisiae mRNA 3'-processing sites.

We present a tool for the prediction of mRNA 3'-processing (cleavage and polyadenylation) sites in the yeast Saccharomyces cerevisiae, based on a discrete state-space model or hidden Markov model. Comparison of predicted sites with experimentally verified 3'-processing sites indicates good agreement. All predicted or known yeast genes were analyzed to find probable 3'-processing sites. Known alternative 3'-processing sites, both within the 3'-untranslated region and within the protein coding sequence were successfully identified, leading to the possibility of prediction of previously unknown alternative sites. The lack of an apparent 3'-processing site calls into question the validity of some predicted genes. This is specifically investigated for predicted genes with overlapping coding sequences.

3' Untranslated Regions↗
PubMed2005

The validity of the Finnish Hospital Discharge Register and Causes of Death Register data on coronary heart disease.

BACKGROUND AND DESIGN: The recent introduction of sensitive markers of myocardial injury is likely to affect the epidemiology of coronary heart disease (CHD). The American Heart Association together with other societies and research agencies have recently published a new definition on acute CHD to improve consistency in epidemiological and clinical studies (referred here as the '2003 definition'). METHODS: In this study we compare the data on CHD events in the Finnish National Hospital Discharge Register (HDR) and the Causes of Death Register (CDR) with the population-based myocardial infarction (MI) register, FINMONICA/FINAMI. The FINMONICA/FINAMI events were classified according to the 2003 definition. The relevant International Classification of Diseases (ICD) codes from the HDR and CDR were used. RESULTS: Using the 2003 definition as the reference, the overall sensitivity of the ICD codes for MI in the combined HDR and CDR was 83% and the positive predictive value (PPV) was 90%. When the ICD codes for unstable angina were added to the analyses, the sensitivity improved to 85% and the PPV declined to 83%. In the age group 35-74 the sensitivity of the MI codes improved over time, in men from 64% in 1988-1992 to 81% in 1998-2002, and in women from 61 to 78%, respectively. The oldest age group, 75 years or older, had sensitivity and PPV values comparable to those of the younger. CONCLUSION: Diagnoses of fatal and non-fatal CHD events in the Finnish HDR and Causes of Death register were reasonably valid indicators for hard CHD events when compared with the FINMONICA/FINAMI register data.

Adult↗
PubMed2006

Prediction of human microRNA targets.

MicroRNAs (miRNAs) are small, nonprotein-coding RNAs that regulate gene expression. Although hundreds of human miRNA genes have been discovered, the functions of most of these are unknown. Computational predictions indicate that miRNAs, which account for at least 1% of human protein-coding genes, regulate protein production for thousands of or possibly all of human genes. We discuss the functions of mammalian miRNAs and the experimental and computational methods used to detect and predict human miRNA target genes. Anticipating their impact on genome-wide discovery of miRNA targets, we describe the various computational tools and web-based resources available to predict miRNA targets.

3' Untranslated Regions↗
PubMed2005

Lack of a centre effect in UK renal units: application of an artificial neural network model.

BACKGROUND: Dialysis centre effect has been suggested to influence survival in end-stage renal disease (ESRD) patients. Few studies over the past decade have commented on the existence of the centre effect using logistic regression models. METHODS: We used high quality prospectively collected data from the UK Renal Registry (UKRR) and created an artificial neural network model to predict mortality within 1 year in this cohort. We used a multitude of demographic variables including co-morbodities as well as relevant laboratory data to create a prognostic model. RESULTS: A highly efficient model for predicting 1 year mortality was created after restricting the model to use demographic and case-enriched data [area under the receiver operating characteristic curve (AUROC) = 0.974]. The addition of the dialysis centre code and centre size as input variables did not add to the efficiency of the model (AUROC = 0.962). Moreover, dialysis centre code or size alone was not predictive of mortality when applied to an artificial neuronal network architecture (AUROC = 0.649 and 0.628). CONCLUSION: Residual effects in previous studies may have been due to the non-linear nature of the data and complex intervariable relationships. Centre size and other centre-related factors have no impact on survival on ESRD.

Aged↗
PubMed1987

Molecular cloning and sequence analysis of two rat major globin cDNAs.

Two cDNA clones for globins of the adult Wistar rat were isolated from a reticulocyte cDNA library and the nucleotide sequences of the inserts were determined. One clone contained a cDNA insert consisting of 556 bp and the other contained one of 577 bp, both covering the entire coding sequences for rat globins. Comparisons of their predicted amino acid sequences with known sequences of rat globins revealed that these cDNAs coded for a rat major alpha- and a major beta-globin, I alpha and II beta, respectively. The cause of diversity of rat globins was discussed in terms of the nucleotide sequences of cDNAs and known amino acid sequences of globins.

Amino Acid Sequence↗
PubMed2002

Estimates of radiological risk from depleted uranium weapons in war scenarios.

Several weapons used during the recent conflict in Yugoslavia contain depleted uranium, including missiles and armor-piercing incendiary rounds. Health concern is related to the use of these weapons, because of the heavy-metal toxicity and radioactivity of uranium. Although chemical toxicity is considered the more important source of health risk related to uranium, radiation exposure has been allegedly related to cancers among veterans of the Balkan conflict, and uranium munitions are a possible source of contamination in the environment. Actual measurements of radioactive contamination are needed to assess the risk. In this paper, a computer simulation is proposed to estimate radiological risk related to different exposure scenarios. Dose caused by inhalation of radioactive aerosols and ground contamination induced by Tomahawk missile impact are simulated using a Gaussian plume model (HOTSPOT code). Environmental contamination and committed dose to the population resident in contaminated areas are predicted by a food-web model (RESRAD code). Small values of committed effective dose equivalent appear to be associated with missile impacts (50-y CEDE < 5 mSv), or population exposure by water-independent pathways (50-y CEDE < 80 mSv). The greatest hazard is related to the water contamination in conditions of effective leaching of uranium in the groundwater (50-y CEDE < 400 mSv). Even in this worst case scenario, the chemical toxicity largely predominates over radiological risk. These computer simulations suggest that little radiological risk is associated to the use of depleted uranium weapons.

Computer Simulation↗
PubMed1983

"Dr. Death" and the case for an ethical ban on psychiatric and psychological predictions of dangerousness in capital sentencing proceedings.

Psychiatric and psychological predictions of dangerousness are used in a number of American jurisdictions to convince a judge or jury that a convicted murderer should be sentenced to death. Empirical research has demonstrated, however, that psychiatric and psychological predictions of dangerousness generally are inaccurate. This Article describes the current use of such predictions in capital sentencing hearings and examines their status under existing professional codes of ethics. It argues that the rendering of these predictions by psychiatrists and psychologists is contrary to the scientific and healing traditions of their professions and urges psychiatrists and psychologists to adopt an ethical ban on predictions of dangerousness in the capital sentencing context.

Capital Punishment↗
PubMed2005

Accurate prediction of the functional significance of single nucleotide polymorphisms and mutations in the ABCA1 gene.

The human genome contains an estimated 100,000 to 300,000 DNA variants that alter an amino acid in an encoded protein. However, our ability to predict which of these variants are functionally significant is limited. We used a bioinformatics approach to define the functional significance of genetic variation in the ABCA1 gene, a cholesterol transporter crucial for the metabolism of high density lipoprotein cholesterol. To predict the functional consequence of each coding single nucleotide polymorphism and mutation in this gene, we calculated a substitution position-specific evolutionary conservation score for each variant, which considers site-specific variation among evolutionarily related proteins. To test the bioinformatics predictions experimentally, we evaluated the biochemical consequence of these sequence variants by examining the ability of cell lines stably transfected with the ABCA1 alleles to elicit cholesterol efflux. Our bioinformatics approach correctly predicted the functional impact of greater than 94% of the naturally occurring variants we assessed. The bioinformatics predictions were significantly correlated with the degree of functional impairment of ABCA1 mutations (r2 = 0.62, p = 0.0008). These results have allowed us to define the impact of genetic variation on ABCA1 function and to suggest that the in silico evolutionary approach we used may be a useful tool in general for predicting the effects of DNA variation on gene function. In addition, our data suggest that considering patterns of positive selection, along with patterns of negative selection such as evolutionary conservation, may improve our ability to predict the functional effects of amino acid variation.

ATP Binding Cassette Transporter 1↗
PubMed1981

Coding theory of visual pattern completion.

It is possible to construct a line drawing that represents one object partly hidden behind another, and most subjects complete the interrupted figure and see the hidden object as whole. This article is addressed to two problems: (a) What are the necessary and sufficient conditions for such figural completion to occur, and (b) exactly what will be seen behind the occluding figure---that is, what completion will be made? Leeuwenberg's coding model for line drawings was used to analyze a number of such figures, along with the hypothesis that figural completion occurs whenever it results in a simplification of final code of the whole figure. Data from previous experiments along with results from two new experimental studies were collected and shown to agree with this hypothesis. Of various possible figural completions or "mosaic" interpretations, subjects chose the ones resulting in the simplest overall code. However, the above conclusions are correct only if "simple" is precisely defined as the smallest information load in a completely reduced code. Other possible theories of figural completion, both structuralist and Gestalt, may invoke familiarity, particular "cues," like T-shaped intersections, simplicity of the hidden figure, symmetry, and good continuation. All such possibilities were considered in the experiments and shown to fail, wrongly predicting at least one figure. The coding-theory analysis, on the other hand, made correct predictions for all of the 25 figures used.

Cues↗
PubMed2004

Neural coding of basic reward terms of animal learning theory, game theory, microeconomics and behavioural ecology.

Neurons in a small number of brain structures detect rewards and reward-predicting stimuli and are active during the expectation of predictable food and liquid rewards. These neurons code the reward information according to basic terms of various behavioural theories that seek to explain reward-directed learning, approach behaviour and decision-making. The involved brain structures include groups of dopamine neurons, the striatum including the nucleus accumbens, the orbitofrontal cortex and the amygdala. The reward information is fed to brain structures involved in decision-making and organisation of behaviour, such as the dorsolateral prefrontal cortex and possibly the parietal cortex. The neural coding of basic reward terms derived from formal theories puts the neurophysiological investigation of reward mechanisms on firm conceptual grounds and provides neural correlates for the function of rewards in learning, approach behaviour and decision-making.

Animals↗
PubMed2002

A theoretical limit to coding space in chromosomes of bacteria.

A mathematical model of cluster patterns for mapped genes with known phenotypes in Escherichia coli predicted thatfunctional genes may account for a maximum of two-thirds of the total chromosomal space. The corollary prediction was that one-third of the chromosome comprised noncoding space. Open reading frame (ORF) analyses for 15 phylogenetically diverse bacterial genomes and for 30 fully sequenced prokaryotic genomes supported the gene cluster model prediction of a two-thirds tendency for coding space. Our results suggest that only 3-4% of unassigned ORFs in E. coli represent genes with potential phenotype and that ORFs marking novel genes in prokaryotes are far fewer than previously thought.

Chromosomes, Bacterial↗
PubMed1994

Organization and sequence of the SalI restriction-modification system.

The organization and nucleotide (nt) sequences were determined for the genes encoding the SalI restriction and modification (R-M) system (recognition sequence 5'-GTCGAC-3') from Streptomyces albus G. The system comprises two genes, salIR, coding for the restriction endonuclease (ENase, R.SalI; probably 315 amino acids (aa), a predicted M(r) of 35,305; product, G'TCGAC) and salIM, coding for the methyltransferase (MTase, M.SalI; probably 587 aa, a predicted M(r) of 64,943; product, GTCGm6AC). The genes are adjacent, they have the same orientation, and they occur in the order salIR then salIM. R.SalI contains a putative magnesium-binding motif similar to those at the active sites of R.EcoRI and R.EcoRV, but otherwise it bears little aa sequence similarity to other ENases. M.SalI is a member of the m6A gamma class of MTases. In aa sequence it resembles M.AccI, another m6A gamma-MTase whose recognition sequence includes the SalI recognition sequence as a subset.

Amino Acid Sequence↗
PubMed2003

Compositional features of eukaryotic genomes for checking predicted genes.

Gene prediction relies on the identification of characteristic features of coding sequences that distinguish them from non-coding DNA. The recent large-scale sequencing of entire genomes from higher eukaryotes, in conjunction with currently used gene prediction algorithms, has provided an abundance of putative genes that can now be analysed for their compositional properties. Strong, systematic differences still exist, in several species, between the compositional properties of sets of ex novo predicted genes and genes that have been experimentally detected and/or verified. This is particularly evident in the estimated gene set (>45,000 genes) of the recently sequenced rice genome, where roughly half the predicted genes are compositionally unusual and have no known orthologues in the dicot Arabidopsis. In a few cases such differences might suggest a bias in experimental gene-finding protocols, but the quasi-random nature of the compositionally aberrant predicted genes is a strong indication that many, if not most, of them are false positives. It therefore appears that some important features of coding regions have not yet been taken into account in existing gene prediction programs. Statistical base compositional properties of curated gene data sets from vertebrates, which we briefly review here, should therefore provide a useful benchmark for fine-tuning probabilistic gene models and model parameters that are currently in use.

Animals↗
PubMed2000

Novel frameshift mutations in the RP2 gene and polymorphic variants.

Mutations in the RP2 gene located on Xp11.23 are associated with X-linked retinitis pigmentosa (XLRP), a severe form of progressive retinal degeneration which leads to complete loss of vision in affected males. To date, 14 different mutations in the RP2 gene have been reported to cause XLRP, the majority of which lead to a coding frameshift within the gene and predicted truncation of the protein product. We here report two novel frameshift mutations in RP2 identified in XLRP families by PCR-SSCP and direct sequencing, namely 723delT and 796-799del. Four single nucleotide polymorphisms (SNPs) within the coding region of RP2 are also described (105A>T, 597T>C, 844C>T, 1012G>T), the first polymorphisms to be reported within this gene of unknown function, two of which alter the amino acid sequence. The current study extends the XLRP mutation profile of RP2 and highlights non-pathogenic coding sequence variations which may facilitate both functional studies of the gene and analysis of intragenic allelic contribution to the phenotype.

Alternative Splicing↗
PubMed2000

Mapping of mRNA transcripts in the genome of molluscum contagiosum virus: transcriptional analysis of the viral slam gene family.

Molluscum contagiosum virus (MCV) is a member of the poxvirus family and causes benign skin tumors in children and immunocompromised individuals. The primary structure and coding capacity of MCV was previously determined by DNA nucleotide sequencing (Senkevich et al., Science 273, 813-816, 1996). Hypothetical genes were predicted based on (i) amino acid homologies with known genes, (ii) presence or absence of conserved transcription regulation signals, and (iii) algorithms based on learning sets of coding sequences. These methods provide a rational basis for the prediction of MCV coding sequences. However, the existence and exact size of MCV open reading frames and the precise position of transcription regulation signals can only be determined by MCV mRNA transcript mapping experiments. We developed methods for the characterization of the mRNA transcripts of MCV genes in infected skin tissue and abortively infected human fibroblast cell cultures. Using these methods the properties of the mRNA transcripts of the MCV SLAM (signaling lymphocytic activating molecule) gene family (mc002L, mc161R, and mc162R) were analyzed. The mRNA start site found for the mc161R transcript suggests that a second start codon is used leading to a mc161R open reading frame that is nine amino acid residues shorter than predicted.

Antigens, CD↗
PubMed2002

Adenylosuccinate lyase of Schistosoma mansoni: gene structure, mRNA expression, and analysis of the predicted peptide structure of a potential chemotherapeutic target.

Adenylosuccinate lyase is an enzyme used in parasite nucleotide salvage pathways that cleaves adenylosuccinate into adenosine 5'-monophosphate and fumarate. A cDNA encoding adenylosuccinate lyase from the trematode parasite Schistosoma mansoni has been cloned for analysis. Sequencing of the cDNA revealed an open reading frame of 1454 nucleotides that codes for a protein with a predicted mass of about 54.5 kDa. Comparative analysis of the predicted protein sequence shows that S. mansoni adenylosuccinate lyase has a lot of similarity with human adenylosuccinate lyase. Genomic analysis using S. mansoni adenylosuccinate lyase-containing bacterial artificial chromosome (BAC) clones revealed a gene of approximately 19.4 kb consisting of eight exons and seven introns. Intron 6 was found to contain a novel 2.9 kb long terminal repeat retrotransposon with direct terminal repeats of 500 nucleotides. Fluorescence in situ hybridisation mapping localised S. mansoni adenylosuccinate lyase to the Z and W chromosomes. Analysis of S. mansoni adenylosuccinate lyase mRNA expression levels using real time reverse transcriptase (RT)-PCR showed that S. mansoni adenylosuccinate lyase is expressed at higher levels in the female worms than in the male worms and is expressed at different levels than other purine nucleotide salvage enzymes. Male homogenate showed a specific activity of 10.3 units/mg protein while the female showed a specific activity of 24.2 units/mg protein. These data indicate that S. mansoni adenylosuccinate lyase is an important parasite enzyme and should be examined as a potential chemotherapeutic target.

Adenylosuccinate Lyase↗