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PubMed2001

Selection of an infectious bursal disease virus mutant with increased immunogenicity following passage under humoral immune pressure.

It is generally known that the pathogenicity of infectious bursal disease virus (IBDV) strains decreases following passage in cell culture. However, there is no information about the effect of passage under immune pressure on the phenotypic and molecular properties of IBDV. In the present study, a small plaque mutant virus with poor neutralization capability, but showing similar growth characteristics as the parental virus strain, QC2, was isolated after serial passage in Vero cells in presence of IBDV serotype 1 chicken polyclonal antiserum. This mutant virus showed reduced pathogenicity but enhanced immunogenicity compared to the parental virus. Sequence analysis of the non-coding regions of the genome revealed 4 and 3 nucleotide changes in the 3' non-coding regions of segments A and B, respectively, and none in the 5' non-coding regions. Restriction enzyme analysis of selected coding regions of the IBDV genome in both viruses revealed a loss of the PstI site in the VP2 region of the mutant virus. Selection of such mutant viruses by passaging under immune pressure may offer an improved method for developing safer and more effective attenuated vaccine strains against infectious bursal disease of chickens.

Animals↗
PubMed2006

Fast rate coding in hippocampal CA3 cell ensembles.

Environments with overlapping features are represented by distinct patterns of activity in the hippocampus, enabling information to be stored and retrieved with minimal interference. This orthogonalization of correlated inputs is thought to take place within the hippocampus itself. However, the orthogonalization process has been shown to take days to develop in CA1. This prolonged time course is in striking contrast to the fast encoding of behavioral memory by the hippocampus. To explore this apparent paradox, we asked whether orthogonalization depended on the type of remapping exhibited by the hippocampal network. We have previously distinguished two types of remapping, global remapping, which results in the activation of different assemblies of place fields, and rate remapping, which encodes differences between cue constellations by substantial changes in firing rate without a change in the place code. Global remapping has previously been shown to be expressed immediately at novel locations. Here we asked if rate remapping follows a slower time course. Ensemble activity was recorded simultaneously from CA3 and CA1 in rats exposed to two similar, novel environments. It was found that rate changes in response to novel sensory cue configurations can form immediately, just as during global remapping, in particular in CA3. The fast encoding of both spatial and nonspatial information in CA3 is consistent with a role for the autoassociative CA3 circuitry in the acquisition and expression of episodic memories.

Action Potentials↗
PubMed1991

[Diabetes mellitus as cause of death].

Certification and coding of diabetes mellitus as a cause of death were investigated by sending a random sample of 300 physicians a set of 6 case histories. Of these, 228 (76%) participated in the study by completing a death certificate for each of these cases. The certificates were subsequently coded by the Central Bureau of Statistics. The main finding was that doctors varied enormously in the way in which diabetes mellitus was mentioned on the death certificate: not at all, as a contributory cause of death, or as an underlying cause of death. Coding removes some of the inconsistencies, but induces additional variation: a higher age of the deceased is associated with a lower probability of having diabetes mellitus coded as the underlying cause of death, and a higher probability of not receiving a code of diabetes mellitus at all. It is concluded that the cause-of-death registration does not provide an accurate picture of the contribution of diabetes mellitus to the cause-of-death pattern of the Netherlands. This is due, amongst other things, to the conceptualization of causes of death on which the registration is based. On the other hand, changes in certification and coding practice within the current system may already lead to some improvement.

Adult↗
PubMed2005

Specificity of sensorimotor learning and the neural code: neuronal representations in the primary motor cortex.

Human studies show that the learning of a new sensorimotor mapping that requires adaptation to directional errors is local and generalizes poorly to untrained directions. We trained monkeys to learn new visuomotor rotations for only one target in space and recorded neuronal activity in the primary motor cortex before, during and after learning. Similar to humans, the monkeys showed poor transfer of learning to other directions, as observed by behavioral aftereffects for untrained directions. To test for internal representations underlying these changes, we compared two features of neuronal activity before and after learning: changes in firing rates and changes in information content. Specific elevations of firing rate were only observed in a subpopulation of cells in the motor cortex with directional properties corresponding to the locally learned rotation; namely cells only showed plasticity if their preferred direction was near the training one. We applied measures from information theory to probe for learning-related changes in the neuronal code. Single cells conveyed more information about the direction of movement and this specific improvement in encoding was correlated with an increase in the slope of the neurons' tuning curve. Further, the improved information after learning enabled a more accurate reconstruction of movement direction from neuronal populations. Our findings suggest a neural mechanism for the confined generalization of a newly acquired internal model by showing a tight relationship between the locality of learning and the properties of neurons. They also provide direct evidence for improvement in the neural code as a result of learning.

Action Potentials↗
PubMed2006

Dynamic synchrony of firing in the monkey prefrontal cortex during working-memory tasks.

Synchronized firing among neurons in the working brain is inferred to reflect coding by cell assemblies, which dynamically change their sizes and functional connections to encode various information. It therefore follows that, if synchronized firing reflects cell-assembly coding, it should show dynamic changes that depend on the tasks and events being processed and on the distance between the neurons. By using unique spike-sorting and multi-neuronal recording methods, we investigated such dynamics of synchrony in the prefrontal cortex of monkeys while they were successively performing two tasks in which working memory for either stimulus duration or color was required. Forty-eight percent of 1405 neuronal pairs showed firing synchrony during the performance of the tasks. Almost half of such neuronal pairs showed fixed synchrony and constantly fired together in both tasks. However, some neuronal pairs showed task-dependent synchrony that appeared in only one of the tasks. Moreover, the other neuronal pairs showed event-task-dependent synchrony that appeared during stimulus or retention periods in the tasks, but the periods showing synchrony varied between the tasks. Fixed synchrony and task-dependent synchrony were mostly observed among neighboring neurons and showed little variation of spike timings; the event-task-dependent synchrony, in contrast, was more often detected among distant neurons with larger variation of spike timings than the other two types of synchrony. These results suggest that some closely neighboring neurons have dynamic and sharp synchrony to represent certain situations (tasks), whereas some distant neurons show more dynamic and unstable synchronous firing to represent quickly changing events being processed in working memory.

Action Potentials↗
PubMed1993

Axonal coding of action potentials in demyelinated nerve fibers.

Conduction in individual axons of Xenopus has been measured optically in response to short trains of stimuli, following demyelination of the sciatic nerve. In many cases the initial action potential in a burst is absent. Failure may also occur later in the train, resulting in a profound alteration of signal coding by the axon. Integration leading to delayed transmission occurred at the heminode forming the proximal border of the demyelinated zone, as well as at new nodes of Ranvier forming in remyelinating axons. This process appeared to involve a depolarizing afterpotential and seemed to be analogous to the threshold changes involved in superexcitability. Axonal coding was very sensitive to small changes in the stimulus pattern. Neither 1 mM tetraethylammonium ion, which blocks nodal and Ca2+ activated K+ channels, nor 1 mM 4-aminopyridine, which blocks fast internodal K+ channels, prevented loss of the initial spike in a burst. Similarly, neither block of Ca2+ channels by Cd2+ nor lowering of Cl- had a notable effect. Ouabain, on the other hand, had small but possibly significant effects on responses to repetitive stimuli. A computational model was used to test mechanisms involving passive cable properties. Lowering the myelin resistance and the nodal leakage conductance, in accord with recent evidence from intracellular recordings, reproduced many of the results and was accurate with respect to stimulus frequency, temperature and sensitivity to average potential. The coding of action potentials observed here may have clinical consequences in demyelinating diseases such as multiple sclerosis.

Action Potentials↗
PubMed1994

The commerce of professional psychology and the new ethics code.

The 1992 version of the American Psychological Association's Ethical Principles of Psychologists and Code of Conduct brings some changes in requirements and new specificity to the practice of psychology. The impact of the new code on therapeutic contracts, informed consent to psychological services, advertising, financial aspects of psychological practice, and other topics related to the commerce of professional psychology are discussed. The genesis of many new thrusts in the code is reviewed from the perspective of psychological service provider. Specific recommendations for improved attention to ethical matters in professional practice are made.

Advertising↗
PubMed2000

Phylogenetic analysis of diatom coxI genes and implications of a fluctuating GC content on mitochondrial genetic code evolution.

In order to address the relationships among diatom groups and to investigate possible changes in their mitochondrial (mt) genetic codes, we have analyzed a 1.1-kb region of the cytochrome c oxidase subunit I (coxI) gene from eight diverse diatom species. A phylogenetic analysis of these coxI sequences including representative species of the Phaeophyta, Xanthophyta, Eustigmatophyta and Haptophyta showed that the diatoms (Bacillariophyta) formed a well-supported monophyletic group. Of the eight species investigated, four have been classified together as radial centric diatoms based on morphology. However, in our coxI tree, the two radial centrics belonging to the order Thlassiosirales (Skeletonema costatum and Thalassiosira nordenskioldii) were placed as the sister group to the multipolar centric diatoms, while the other two radial centrics (Melosira ambigua and Rhizosolenia setigera) were in another clade. Also, in two species of the Tharassiosirales we found UGA codons that occur at conserved tryptophan (Trp) sites in the coxI sequences, strongly indicating that UGA codes for Trp in these diatoms. No evidence of a deviant genetic code was detected in the other analyzed diatom species. There was no apparent relationship between the nucleotide third-position GC content of mtDNA (based on the sequenced coxI region) and the presence of a deviant genetic code.

Base Composition↗
PubMed2006

Effect of copper exposure on gene expression profiles in Chlamydomonas reinhardtii based on microarray analysis.

Copper is a naturally occurring trace metal with toxic properties for man and environment. It is assumed that toxicity is primarily caused by oxidative damage, generated through the production of reactive oxygen species. Copper is, however, also an essential element, which means trace amounts are necessary for biological processes to function properly. Organisms are therefore presented with the challenging problem of maintaining copper concentrations within a well-defined range to avoid stress. We exposed the green alga Chlamydomonas reinhardtii to different copper concentrations and used microarray analysis to investigate the changes in mRNA abundances and to obtain an image of the molecular mechanisms underlying copper homeostasis. The results confirm and extend upon previous findings showing that in the case of lower copper concentrations there is a change in levels of mRNA coding for alternative polypeptides which can take over the function of certain copper containing molecules so as to compensate for the lack of copper. In the case of copper toxicity, there is a strong upregulation of transcripts encoding enzymes involved in oxidative stress defense mechanisms. In both cases, there were significant changes in expression levels of transcripts coding for enzymes involved in several metabolic pathways (photosynthesis, pentose phosphate pathway, glycolysis, gluconeogenesis), in general stress response (heat shock proteins) and in intracellular proteolysis (lysosomal enzymes, proteasome components).

Algal Proteins↗
PubMed2004

Role of spike timing in the forelimb somatosensory cortex of the rat.

The aim of this study was to test the hypothesis that the significance of spike timing in somatosensory processing is not a specific feature of the whisker cortex but a more general characteristic of the primary somatosensory cortex. We recorded ensembles of neurons using microwire arrays implanted in the deep layers of the forelimb region of the rat primary somatosensory cortex in response to step stimuli delivered to the cutaneous surface of the contralateral body. We used a recently developed peristimulus time histogram (PSTH)-based classification method to investigate the temporal precision of the code by evaluating how changing the bin size (from 40 to 1 msec) would affect the ability of the ensemble responses to discriminate stimulus location on a single-trial basis. The information related to the discrimination was redundantly distributed within the ensembles, and the ability to discriminate stimulus location increased when decreasing the bin size, reaching a maximum at 4 msec. In our experiment, at 4 msec bin size the first spike per neuron after the stimulus conveyed almost as much information as the entire responses, so the temporal precision of the code was preserved in the first spikes. Subsequent spikes were less frequent but conveyed more information per spike. Finally, not only the trials correctly classified but also the trials incorrectly classified conveyed information about stimulus location with a similar temporal precision. We conclude that the role of spike timing in cortical somatosensory processing is not an exclusive feature of the highly specialized rat trigeminal system, but a more general property of the rat primary somatosensory cortex.

Action Potentials↗
PubMed1995

Objective speech quality assessment and the RPE-LTP coding algorithm in different noise and language conditions.

The formulation of reliable signal processing algorithms for speech coding and synthesis require the selection of a prior criterion of performance. Though coding efficiency (bits/second) or computational requirements can be used, a final performance measure must always include speech quality. In this paper, three objective speech quality measures are considered with respect to quality assessment for American English, noisy American English, and noise-free versions of seven languages. The purpose is to determine whether objective quality measures can be used to quantify changes in quality for a given voice coding method, with a known subjective performance level, as background noise or language conditions are changed. The speech coding algorithm chosen is regular-pulse excitation with long-term prediction (RPE-LTP), which has been chosen as the standard voice compression algorithm for the European Digital Mobile Radio system. Three areas are considered for objective quality assessment which include: (i) vocoder performance for American English in a noise-free environment, (ii) speech quality variation for three additive background noise sources, and (iii) noise-free performance for seven languages which include English, Japanese, Finnish, German, Hindi, Spanish, and French. It is suggested that although existing objective quality measures will never replace subjective testing, they can be a useful means of assessing changes in performance, identifying areas for improvement in algorithm design, and augmenting subjective quality tests for voice coding/compression algorithms in noise-free, noisy, and/or non-English applications.

Adult↗
PubMed1992

Evolution of the H3 influenza virus hemagglutinin from human and nonhuman hosts.

The nucleotide and amino acid sequences of 40 influenza virus hemagglutinin genes of the H3 serotype from mammalian and avian species and 9 genes of the H4 serotype were compared, and their evolutionary relationships were evaluated. From these relationships, the differences in the mutational characteristics of the viral hemagglutinin in different hosts were examined and the RNA sequence changes that occurred during the generation of the progenitor of the 1968 human pandemic strain were examined. Three major lineages were defined: one containing only equine virus isolates; one containing only avian virus isolates; and one containing avian, swine, and human virus isolates. The human pandemic strain of 1968 was derived from an avian virus most similar to those isolated from ducks in Asia, and the transfer of this virus to humans probably occurred in 1965. Since then, the human viruses have diverged from this progenitor, with the accumulation of approximately 7.9 nucleotide and 3.4 amino acid substitutions per year. Reconstruction of the sequence of the hypothetical ancestral strain at the avian-human transition indicated that only 6 amino acids in the mature hemagglutinin molecule were changed during the transition between an avian virus strain and a human pandemic strain. All of these changes are located in regions of the molecule known to affect receptor binding and antigenicity. Unlike the human H3 influenza virus strains, the equine virus isolates have no close relatives in other species and appear to have diverged from the avian viruses much earlier than did the human virus strains. Mutations were estimated to have accumulated in the equine virus lineage at approximately 3.1 nucleotides and 0.8 amino acids per year. Four swine virus isolates in the analysis each appeared to have been introduced into pigs independently, with two derived from human viruses and two from avian viruses. A comparison of the coding and noncoding mutations in the mammalian and avian lineages showed a significantly lower ratio of coding to total nucleotide changes in the avian viruses. Additionally, the avian virus lineages of both the H3 and H4 serotypes, but not the mammalian virus lineages, showed significantly greater conservation of amino acid sequence in the internal branches of the phylogenetic tree than in the terminal branches. The small number of amino acid differences between the avian viruses and the progenitor of the 1968 pandemic strain and the great phenotypic stability of the avian viruses suggest that strains similar to the progenitor strain will continue to circulate in birds and will be available for reintroduction into humans.

Amino Acid Sequence↗
PubMed1985

Copy mutant of mini-Rts1: lowered binding affinity of mutated RepA protein to direct repeats.

Nucleotide sequence analysis of mini-Rts1 and its copy mutant disclosed the presence of two clusters of direct-repeat sequences flanking the coding region for the 33,000-dalton RepA protein and two base substitutions on the mini-Rts1cop1 genome (Kamio et al., J. Bacteriol. 158:307-312, 1984). On subcloning of the left cluster (incI) that is located downstream from repA, the five 24-base-pair repeats expressed a stronger incompatibility toward mini-Rts1 than did the four repeats. The right cluster (incII) that contains three 21-base-pair repeats also exhibited strong incompatibility toward mini-Rts1. By separating the two base substitutions of mini-Rts1cop1, the mutation that is responsible for the copy increase was determined to be a single base change in the RepA coding region. Both clusters of the repeats, cloned separately into the vector plasmid, showed a weaker incompatibility toward mini-Rts1cop1 than to the wild-type mini-Rts1. These findings suggest a lowered binding affinity of the mutated RepA protein to the direct repeats.

Adenosine Triphosphatases↗
PubMed1988

Genetic basis of resistance to rimantadine emerging during treatment of influenza virus infection.

The emergence of influenza A viruses which had acquired resistance to rimantadine during a clinical trial (C. B. Hall, R. Dolin, C. L. Gala, D. M. Markovitz, Y. Q. Zhang, P. H. Madore, F. A. Disney, W. B. Talpey, J. L. Green, A. B. Francis, and M. E. Pichichero, Pediatrics 80:275-282, 1987) provided the opportunity to determine the genetic basis of this phenomenon. Analysis of reassortant viruses generated with a resistant clinical isolate (H3N2) and the susceptible influenza A/Singapore/57 (H2N2) virus indicated that RNA segment 7 coding for matrix and M2 proteins conferred the resistant phenotype. Resistant viruses isolated from seven patients each contained a single change in the nucleotide sequence coding for the M2 protein which resulted in substitutions in amino acid 30 (two viruses) or 31 (five viruses) in the transmembrane domain of the molecule. These changes occurred in locations identified in influenza viruses selected for resistance to amantadine in tissue culture and indicate a common mechanism of action of the two compounds in cell culture and during chemotherapeutic use.

Adamantane↗
PubMed2002

Exact mapping of prokaryotic gene starts.

It is known that while the programs used to find genes in prokaryotic genomes reliably map protein-coding regions, they often fail in the exact determination of gene starts. This problem is further aggravated by sequencing errors, most notably insertions and deletions leading to frame-shifts. Therefore, the exact mapping of gene starts and identification of frame-shifts are important problems of the computer-assisted functional analysis of newly sequenced genomes. Here we review methods of gene recognition and describe a new algorithm for correction of gene starts and identification of frame-shifts in prokaryotic genomes. The algorithm is based on the comparison of nucleotide and protein sequences of homologous genes from related organisms, using the assumption that the rate of evolutionary changes in protein-coding regions is lower than that in non-coding regions. A dynamic programming algorithm is used to align protein sequences obtained by formal translation of genomic nucleotide sequences. The possibility of frame-shifts is taken into account. The algorithm was tested on several groups of related organisms: gamma-proteobacteria, the Bacillus/Clostridium group, and three Pyrococcus genomes. The testing demonstrated that, dependent or a genome, 1-10 per cent of genes have incorrect starts or contain frame-shifts. The algorithm is implemented in the program package Orthologator-GeneCorrector.

Algorithms↗
PubMed2004

Differential regulation of gene expression by RNA polymerase II in response to DNA damage.

Cells change their gene expression profile dynamically in various conditions. By taking the advantage of ChIP, we examined the transcription profile of Saccharomyces cerevisiae genes in response to DNA damaging agents such as MMS or 4NQO. Gene expression profiles of different groups of genes roughly correlated with that revealed by Northern blot assay or microarray method. Damage-inducible genes showed increased cross-linking signals of RNA polymerase II, TFIIH, and TFIIF, meanwhile damage repressible genes decreased them, which means that gene expression is mainly regulated at the level of transcription. Interestingly, the characteristic occupancy pattern of TFIIH and polymerase with phosphorylated carboxy-terminal domain (CTD) in promoter or in coding regions was not changed by the presence of DNA damaging agents in both non-inducible and inducible genes. ChIP data showed that the extent of phosphorylation of CTD per elongating polymerase complex was still maintained. These findings suggest that overall increase in CTD phosphorylation in response to DNA damage is attributed to the global shift of gene expression profile rather than modification of specific polymerase function.

4-Nitroquinoline-1-oxide↗
PubMedDate not supplied

Development and psychometric evaluation of the Environment-Behavior Interaction Code (EBIC).

BACKGROUND: Although the behavioral changes with progressive dementia are seen to increasingly depend on the environmental context until late stage disease, measurement has not reflected this interaction in real time to allow examination of antecedents to disruptive behavior. OBJECTIVES: To develop and evaluate the psychometric properties of the Environment-Behavior Interaction Code (EBIC) for use in dementia care research with either sequential or nonsequential analyses of behavioral data. METHOD: Development of the computer-based (sequential event format) EBIC provided an observational coding system to classify all behavior and environmental context in real time, so that the probability of social environmental antecedents to resident disruptive behavior could be estimated. A checklist (interval format) EBIC, based on the same behavioral taxonomy, was developed for clinical outcome research. A total of 158 elderly residents of dementia care units were purposively selected from three large long-term care facilities for the psychometric study components. RESULTS: Psychometric results indicated significant (p < 0.01) known-groups validity for the disruptive behavior construct, which was defined as a composite of aversive, harmful, and high intensity neutral behavior. Interrater agreement for the event format of the EBIC was estimated by average kappa (0.65) and percentage agreement (78%). For the interval format, the mean interrater kappa was 0.80 with 96% agreement. Stability of the event format using a 2-week retest interval ranged from r= .50 (positive behavior) to r = 0.73 (negative behavior, defined as aversive + harmful). On replication with a new sample, stability was higher for positive (r = 0.92) and negative (r = 0.95) components, and for composite scores of nondisruptive (positive + low intensity neutral; r = 0.65) and disruptive (r= 0.85) behavior. CONCLUSION: This research provided support for the reliability and validity of both event and interval EBIC formats. Measurement using the EBIC taxonomy has applicability to dementia care research questions that call for either sequential analysis of social interactions or nonsequential analysis of behavioral outcomes in intervention studies.

Aged↗
PubMed2002

IntI2 integron integrase in Tn7.

Integrons can insert and excise antibiotic resistance genes on plasmids in bacteria by site-specific recombination. Class 1 integrons code for an integrase, IntI1 (337 amino acids in length), and are generally borne on elements derived from Tn5090, such as that found in the central part of Tn21. A second class of integron is found on transposon Tn7 and its relatives. We have completed the sequence of the Tn7 integrase gene, intI2, which contains an internal stop codon. This codon was found to be conserved among intI2 genes on three other Tn7-like transposons harboring different cassettes. The predicted peptide sequence (IntI2*) is 325 amino acids long and is 46% identical to IntI1. In order to detect recombination activity, the internal stop codon at position 179 in the parental allele was changed to a triplet coding for glutamic acid. The sequences flanking the cassette arrays in the class 1 and 2 integrons are not closely related, but a common pool of mobile cassettes is used by the different integron classes; two of the three antibiotic resistance cassettes on Tn7 and its close relatives are also found in various class 1 integrons. We also observed a fourth excisable cassette downstream of those described previously in Tn7. The fourth cassette encodes a 165-amino-acid protein of unknown function with 6.5 contiguous repeats of a sequence coding for 7 amino acids. IntI2*179E promoted site-specific excision of each of the cassettes in Tn7 at different frequencies. The integrases from Tn21 and Tn7 showed limited cross-specificity in that IntI1 could excise all cassettes from both Tn21 and Tn7. However, we did not observe a corresponding excision of the aadA1 cassette from Tn21 by IntI2*179E.

3' Untranslated Regions↗