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Behavioral correlates of the distributed coding of spatial context.

Hippocampal place cells respond heterogeneously to elemental changes of a compound spatial context, suggesting that they form a distributed code of context, whereby context information is shared across a population of neurons. The question arises as to what this distributed code might be useful for. The present study explored two possibilities: one, that it allows contexts with common elements to be disambiguated, and the other, that it allows a given context to be associated with more than one outcome. We used two naturalistic measures of context processing in rats, rearing and thigmotaxis (boundary-hugging), to explore how rats responded to contextual novelty and to relate this to the behavior of place cells. In experiment 1, rats showed dishabituation of rearing to a novel reconfiguration of familiar context elements, suggesting that they perceived the reconfiguration as novel, a behavior that parallels that of place cells in a similar situation. In experiment 2, rats were trained in a place preference task on an open-field arena. A change in the arena context triggered renewed thigmotaxis, and yet navigation continued unimpaired, indicating simultaneous representation of both the altered contextual and constant spatial cues. Place cells similarly exhibited a dual population of responses, consistent with the hypothesis that their activity underlies spatial behavior. Together, these experiments suggest that heterogeneous context encoding (or "partial remapping") by place cells may function to allow the flexible assignment of associations to contexts, a faculty that could be useful in episodic memory encoding.

Action Potentials↗

Hemoglobin biosynthesis in Vitreoscilla stercoraria DW: cloning, expression, and characterization of a new homolog of a bacterial globin gene.

In the strictly aerobic, gram-negative bacterium Vitreoscilla strain C1, oxygen-limited growth conditions create a more than 50-fold increase in the expression of a homodimeric heme protein which was recognized as the first bacterial hemoglobin (Hb). The recently determined crystal structure of Vitreoscilla Hb has indicated that the heme pocket of microbial globins differs from that of eukaryotic Hbs. In an attempt to understand the diverse functions of Hb-like proteins in prokaryotes, we have cloned and characterized the gene (vgb) encoding an Hb-like protein from another strain of Vitreoscilla, V. stercoraria DW. Several silent changes were observed within the coding region of the V. stercoraria vgb gene. Apart from that, V. stercoraria Hb exhibited interesting differences between the A and E helices. Compared to its Hb counterpart from Vitreoscilla strain C1, the purified preparation of V. stercoraria Hb displays a slower autooxidation rate. The differences between Vitreoscilla Hb and V. stercoraria Hb were mapped onto the three-dimensional structure of Vitreoscilla Hb, which indicated that the four changes, namely, Ile7Val, Ile9Thr, Ile10Ser, and Leu62Val, present within the V. stercoraria Hb fall in the region where the A and E helices contact each other. Therefore, alteration in the relative orientation of the A and E helices and the corresponding conformational change in the heme binding pocket of V. stercoraria Hb can be correlated to its slower autooxidation rate. In sharp contrast to the oxygen-regulated biosynthesis of Hb in Vitreoscilla strain C1, production of Hb in V. stercoraria has been found to be low and independent of oxygen control, which is supported by the absence of a fumarate and nitrate reductase regulator box within the V. stercoraria vgb promoter region. Thus, the regulation mechanisms of the Hb-encoding gene appear to be quite different in the two closely related species of Vitreoscilla. The relatively slower autooxidation rate of V. stercoraria Hb, lack of oxygen sensitivity, and constitutive production of Hb suggest that it may have some other function(s) in the cellular physiology of V. stercoraria DW, together with facilitated oxygen transport, predicted for earlier reported Vitreoscilla Hb.

Amino Acid Sequence↗

Multiple missense mutations in the diazepam binding inhibitor (DBI) gene identified in schizophrenia but lack of disease association.

The diazepam binding inhibitor (DBI), alternatively known as the acyl-CoA binding protein (ACBP), is involved in multiple biological actions. The polypeptide binds to the peripheral, or mitochondrial, benzodiazepine receptor and facilitates transport of cholesterol to the inner membrane to stimulate steroid synthesis. Through this action, DBI indirectly modulates gamma-aminobutyric acid (GABA)-mediated inhibitory neurotransmission. DBI can be postulated as a candidate gene for psychiatric phenotypes including anxiety, mood, and psychotic disorders. In an examination of the DBI gene among 112 individuals with schizophrenia, our laboratory has identified 18 novel single nucleotide polymorphisms (SNPs), including three missense changes in conserved amino acids, a coding region microdeletion, and multiple SNPs in the putative promoter region. Case-control association analyses were performed for the missense changes, but none was found to be significantly associated with disease.

DNA Primers↗

Cell-surface changes induced by ectopic expression of the murine homeobox gene Hox-3.3.

Murine homeobox-containing genes (Hox genes) are postulated as playing key roles in the establishment of the anterior-posterior embryonic body axis, possibly providing cells with positional cues. Little is known, however, concerning how cells might respond to homeobox gene expression to interpret these cues. Since changes in the cell-surface are central to many processes in early development we reasoned that cells expressing different complements of Hox genes might have different surface properties. In order to investigate this we have used the sensitive, non-disruptive technique of multiple two-phase aqueous partition, which is able to detect small differences on the surface of intact cells. Using this technique we have found that ectopic expression of the murine Hox-3.3 gene in cultured cells induces reproducible changes in the cell surface. Changes only occurred above a threshold level of gene expression, but above this level a correlation between surface change and gene expression was seen. The implications for the establishment of a 'Hox' code of homeobox genes acting to specifically change cell-surface properties are discussed.

Animals↗

The high affinity murine laminin receptor is a member of a multicopy gene family.

The high affinity laminin receptor is differentially expressed in metastasis. We now report that there are multiple copies (6 +/- 1) of the laminin receptor gene in the murine genome of normal diploid cells as well as in cell lines derived from cancer cells. We have analyzed three distinct cDNA clones isolated from an Okayama-Berg cDNA library of transformed mouse fibroblasts that may represent transcripts of three different laminin receptor genes. Polymorphic changes include insertion of bases at the 5' terminus, a base substitution within the coding region resulting in an amino acid change from phenylalanine to leucine, a base substitution obliterating a polyadenylation signal, as well as changes in the length of the 3' untranslated domains. The discovery of multiple transcripts of laminin receptor genes suggests that there is a strong selective pressure to maintain laminin receptor expression in murine cells.

Animals↗

A coding scheme for the evaluation of the relationship in music therapy sessions.

This study presents a coding system for observation and monitoring of changes in the interactive behaviour between patient and therapist during music therapy sessions. The coding scheme was developed from a psychodynamic framework and mainly consists of four behavioural classes: Verbal Communication, Nonverbal Communication, Countenance, and Sonorous Musical Communication. The 15 minutes in the middle of each videotape concerning the first active music therapy session--based on the sonorous musical improvisation--were coded. Subjects were children (4 boys; 3 girls) ages 3 to 10 years (M age = 6.3), diagnosed with Pervasive Developmental Disorder, and seven therapists. The method for data collection was continuous recording, applied through The Observer Video-Pro 5.0. For the reliability indexes there was a substantial agreement between assessments by video raters.

Autistic Disorder↗

[Expert witness and expert testimony in New Slovak Criminal Procedure Code].

As of 1st January 2006, new criminal law consisting of the Act No. 300/2004 Coll. (Penal Code) and the Act No. 301/2005 Coll. (Criminal Procedure Code) became effective in the Slovak Republic. These two acts replaced Criminal Law originating from 1961. The author analyses impact and changes introduced with new Criminal Procedure Code in the regulation of expert witness in general and expert witness testimony.

Criminal Law↗

[Populations of behavior-reactive neurons in the monkey neostriatum].

Comparative analysis of the unit activity of the monkey putamen during multistage behavior showed that neurons of the putamen are active during all the behavioral actions. It was established that the number of the behavior-related neurons changes considerably less than number of neurons which reorganize their activity at the time. Reorganization of unit activity in the putamen is considered as reflecting the efferent code which controls behavior, and the degree of reorganization--as a measure of change of this code in relation to organization of ongoing behavioral action. It has been discovered that the change in the number of the active neurons at various steps of behavior and reorganization of their activity occurs independently. It may be related to two main afferent systems of striatum: ascending from rhe brain stem, and corticofugal which brings differentiated information to the neuronal net of striatum from various parts of the cortex.

Action Potentials↗

Global incorporation of unnatural amino acids in Escherichia coli.

The incorporation of amino acid analogs is becoming increasingly useful. Site-specific incorporation of unnatural amino acids allows the application of chemical biology to protein-specific investigations and applications. However, the global incorporation of unnatural amino acids allows for tests of proteomic and genetic code hypotheses. For example, the adaptation of organisms to unnatural amino acids may lead to new genetic codes. To understand and quantify changes from such perturbations, an understanding is required of the microbiological and proteomic responses to the incorporation of unnatural amino acids. Here we describe protocols to characterize the effects of such proteome-wide perturbations.

Amino Acids↗

Querying the ill-defined stroke diagnoses on death certificates and their effects on type-specific mortality in Taiwan.

In Taiwan, the high proportion of stroke deaths of which the underlying causes of death (UCD) has been classified to ill-defined categories, has impeded valid type-specific mortality studies. The aim of this study was to assess the extent of changes in the distributions of stroke subtypes and mortality after querying the certifying physicians. There were 2632 death certificates issued from January through June 1998 in Taiwan of which the UCD was classified to ill-defined cerebrovascular disease categories (International Classification of Diseases, 9th Revision ICD-9 code 436 or 437.9). Staff of the Office of Statistics, Department of Health copied 2035 death certificates issued by hospitals and mailed them back to the certifying physicians to request more specific information on the stroke subtype. Responses were obtained for 1505 (74%) of the 2035 queries sent. Four fifths of these (1191/1505) resulted in a change to a more specific code. In most cases, the ICD-9 code was changed to 431 (cerebral hemorrhage, CH, 239/1505) or 433-4 (cerebral infarction, CI, 819/1505). After the querying, the percentage changes in the age-adjusted death rate (per 100,000 population) for CH were +16% for men and +20% for women; and for CI the percent changed were +100% for men and +130% for women. The changes increased as the age of the deceased increased. The changes in the CH/CI death ratios resulting from querying were greater in younger (less than 65 years old) age groups than in older age groups. Given the large gains of more specific information on stroke subtypes, querying is a useful method to improve the quality of cause of death statistics. However, the large changes in distributions and death rates of different stoke subtypes as a result of querying, show the non-querying mortality data are not suitable for type-specific analysis.

Adult↗

Extraordinarily high evolutionary rate of pseudogenes: evidence for the presence of selective pressure against changes between synonymous codons.

Comparisons of nucleotide sequences of several pseudogenes described to date, including alpha- and beta-globin and immunoglobulin kappa-type variable domain pseudogenes, with those of functional counterparts revealed that pseudogenes accumulate mutations at an extremely high rate uniformly over their entirety. It is remarkable that the evolutionary rate exceeds the rate of changes between synonymous codons, the highest known rate, in functional genes. Because no pseudogenes appear to function, this result strongly supports the neutral theory. In addition this result apparently indicates the presence of selective pressure against changes between synonymous codons in functional genes. Close examinations of codon utilization patterns in pseudogenes and functional genes revealed a significant correlation between the rate of changes at synonymous codon sites and the strength of bias in code word usage. This implies that even synonymous codon changes are not completely free from selective pressure but are constrained in part, although presumably weakly, depending on the degree of bias in code word usage. We also reexamined alignment between mouse beta h3 (pseudogene) and beta maj sequences and found a unique structure of the beta h3 that is homologous in sequence to the beta maj gene overall but contains a long deletion (about 150 base pairs) in the middle of the gene.

Animals↗

Switching between the forest and the trees: brain systems involved in local/global changed-level judgments.

Visual targets can be coded, in relative terms, at either the local or the global level of stimuli. Previous studies have indicated that targets are identified more slowly when they appear at a new hierarchical level, compared to when they reappear at the same level as in the previous trial. In the present study, we used measures of reaction time and event-related fMRI to investigate factors affecting this switch cost. In particular, we examined the effects of the number of repeated-level trials preceding a switch and whether the cue to switch was either externally or internally mediated. At the behavioral level we found that (1) the time taken to identify a target on a changed-level trial is longer following four repeated-level trials compared to two repeated-level trials, but that runs of six do not produce additional costs over four, and (2) targets can be identified faster following externally cued switches compared to internally mediated switches. We then show that these behavioral effects are associated with distinct patterns of neural activation. Switches performed after two repeated-level trials preferentially activated the precuneus, while those performed after both four and six activated bilateral inferior parietal cortex and motor hand area. Relative to external switches, internal switches activated the putamen, while both kinds of switch conjointly activated the large-scale network proposed to underlie internal/external switches in nonhierarchical tasks. Our data further clarify the mechanisms mediating hierarchical selection.

Adult↗

Consecutive actions of different gene-altering mechanisms in the evolution of involucrin.

During the evolution of primates from nonprimates, the gene for involucrin was greatly altered by changes in the short tandem repeats that are present in some form in the gene of each of 17 species examined. The evolution of involucrin was not the result of a single continuum of more or less random changes, and it was not confined to the process of nucleotide substitution, the most commonly studied evolutionary change in DNA. Instead, the evolution of this gene took place through different mechanisms that shortened the length of the repeats, increased their number, and changed their codon sequence. As part of this trend, one entire segment of repeats was replaced by another located elsewhere in the coding region. To bring about these changes, specific mechanisms have been activated, deactivated, and replaced by other mechanisms. The resulting serial revisions in the involucrin gene must depend on gene-altering machinery whose synthesis or activity can be controlled.

Amino Acid Sequence↗

Amino acid composition of proteins as a product of molecular evolution.

The average amino acid composition of proteins is determined by the genetic code and by random base changes in evolution. Small but significant deviations from expected composition can be explained by selective constraint on amino acid substitutions. In particular, the deficiency of arginine in proteins has been caused by constraint, during evolution, on fixation of mutations substituting arginine for other amino acids.

Amino Acids↗

[Research code at the Academic Medical Center in Amsterdam: useful].

At the Academic Medical Centre (AMC) of the University of Amsterdam, the Netherlands, it was decided to set up a research code committee. The first thing that was done was to define what were considered the most relevant types of scientific misconduct: falsification, plagiarism and invasion of privacy. The committee decided that prevention is better than cure and therefore developed a guideline for desirable behaviour, i.e. how to act scientifically with care and integrity, instead of a guideline on what not to do. The committee also proposed an ombudsman whose services are available to all participants in research in the AMC, and to whom misconduct can be reported. The research code is a loose-leaf system, since new issues will come to the fore and included issues will need to be changed. This committee has created a code that provides a firm basis for scientific integrity within the AMC.

Ethics, Research↗

The dynamics of spatiotemporal response integration in the somatosensory cortex of the vibrissa system.

Spatiotemporal response integration across the neural receptive field (RF) is a general feature of sensory coding and has an important role in shaping responses to naturalistic stimuli. In the primary somatosensory cortex of the rat vibrissa pathway, such integration across the vibrissa array strongly shapes the coding of spatiotemporally distributed deflections. Using a spatiotemporal paired-pulse paradigm, this study revealed that fundamentally different types of pairwise interactions have similar qualitative behavior but that the magnitude, latency, and precision of the neural responses depend on the specific RF components being engaged. In all cases, however, increase in the suppression of response magnitude accompanied a lengthening of latency and a decrease in response precision. Furthermore, nonlinear interactions evoked by stimulation of multiple RF subregions strongly influence both response magnitude and timing to more complex sequences. Despite their complexity, such response interactions are highly predictable from elementary pairwise interactions. To understand the functional role of spatiotemporal interactions in coding, we developed a response model that incorporated the experimentally measured modulations in response magnitude, latency, and precision induced by cross-vibrissa interactions. Simulations of a simplified textural discrimination task indicate that spatiotemporal interactions enhance discrimination under certain stimulus time scales. This improvement follows from a nonlinear response property that acts to restore the neural response in the face of suppression. Together, the present findings highlight the role of response integration in shaping single-cell responses and provide predictions about how changes in response parameters influence coding accuracy.

Action Potentials↗

Ethical codes in nursing practice: the viewpoint of Finnish, Greek and Italian nurses.

AIM: This paper is a report of a study exploring the use of ethical codes and obstacles to their use in nursing practice as perceived by Finnish, Greek and Italian nurses. BACKGROUND: In all European countries nurses are responsible for the well-being of patients, for their own technical and ethical competence and, for their own part, for the high standard of health care in society. These points illustrate the central content areas of nursing codes of ethics. Recent advances in medical technology have added to the complexity of nursing. Nurses today are increasingly confronted with ethical dilemmas, underlining the role and meaning of ethical codes in their decision-making. However, there is only very limited research literature on codes of ethics, their use in nursing practice and obstacles to their use. METHODS: Twenty-three focus group interviews were conducted in 2003 with a total of 138 Registered Nurses: 35 in Finland, 54 in Greece and 49 in Italy. The data were content analysed. FINDINGS: Two main categories emerged from our analysis of the use of ethical codes: (1) conscious and (2) unconscious use. Seven main categories described the obstacles to the use of ethical codes: (1) the codes themselves, (2) nurses themselves, (3) multiprofessional teamwork, (4) patients' family members, (5) the organization, (6) the nursing profession and (7) society/healthcare policy. Participants in all three countries were firmly committed to the values expressed in ethical nursing codes. Nonetheless, continued efforts are needed in all these countries to remove the remaining obstacles so that nursing care can be provided in keeping with the requirements of ethical codes. CONCLUSION: The use of codes is connected with the changes in nursing profession and in society at large. The core of nursing, however, has remained stable. Future studies should be conducted in order to generalize the findings to a broader population.

Adult↗

The sequences of genes bordering oriT in the enterotoxin plasmid P307: comparison with the sequences of plasmids F and R1.

The nucleotide sequences of the enterotoxin plasmid P307 transfer genes traM, finP, traJ, traY, and gene 19 were determined. Gene 19 is highly conserved; its product is very similar to that coded by the F and R1 plasmids. The TraM protein is similar in P307 and in F; the R1 sequence shows differences in the 40 N-terminal amino acids. The traJ product is very different in P307, F, and R1. The traY gene from P307, which in F is almost twice as long, is similar in size to that from R1. The finP RNA shows a high degree of homology with that from R1 and F, except for the two loop regions where base changes were observed. The genes coding for proteins, except traY, could be expressed in minicell- and T7 promoter-driven expression systems, whereas traJ and gene 19 could be expressed only in the latter system.

Amino Acid Sequence↗