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At least 1,441 records · Page 80Linked to original sources
PubMed2005

Evolution of hepatitis delta virus RNA genome following long-term replication in cell culture.

Previous studies have defined a novel cell culture system in which a modified RNA genome of hepatitis delta virus (HDV) is able to maintain a low level of continuous replication for at least 1 year, using a separate and limited DNA-directed source of mRNA for the essential small delta protein. This mode of replication is analogous to that used by plant viroids. An examination was made of the nucleotide changes that accumulated on the HDV RNA during 1 year of replication. The length of the RNA genome was maintained, except for some single-nucleotide deletions and insertions. There was an abundance of single-nucleotide substitutions, with a 22-fold excess of these being base transitions rather than transversions. Of the detected transitions, at least 70% were consistent with being the consequences of posttranscriptional RNA editing by an adenosine deaminase acting on RNA. The remainder of the changes, including the single-nucleotide insertions and deletions, are likely to be the consequence of misincorporation during transcription. In addition, an intermolecular competition assay was used to show that the majority of the genomes present after 1 year of replication were essentially as competent in replication as the original single HDV RNA sequence that was used to initiate the genome replication. A model is provided to explain how, in this experimental system, the observed single-nucleotide changes were essentially neutral in terms of their effect on the ability of the HDV genome to carry out continued rounds of replication.

Base Sequence↗
PubMed2002

[Studies on "Ishin shoden" Edited by Dosan Manase (1507-1594): the introduction of Satsusho Benchi and the process of its establishment].

Sanki Tashiro and Dosan Manase are known for their role as founders of the Gosei-ha school in Japan. Observing that Japanese medicine had not been based on a clear theory, they introduced into Japan the satsusho benchi practiced in Chinese medicine during the Jin and Yuan dynasties. The basis of this system was to examine the patient's condition, then determine the treatment accordingly. Dosan Manase in particular employed the satsusho benchi, writing out a new prescription each time treatment was required, without reference to existing prescriptions. In this study, we carried out an investigation into the "Ishin shoden"edited by Dosan Manase, which reveals the process by which Dosan established the new satusho benchi system of medicine within the framework of traditional Japanese medicine. In the early stages of the process, Dosan prepared prescriptions based on existing iou-tou prescriptions, modifying these by adding or removing medicines. Then, in the middle period, he prepared prescriptions based on toso-tou prescriptions, designed on the basis of the kun shin sa shi or Junchen Zuoshi theory, again modifying these by adding or removing medicines. In the final stage of the process, Dosan ceased this practice of adding or removing medicines from a basic prescription, adopting instead the satusho benchi system of writing out a new prescription for every treatment. In addition, we consider the reasons why the satusho benchi system was not employed by Dosan's successors, and discuss the effects of this.

Drug Prescriptions↗
PubMed2001

Improved spin-echo-edited NMR diffusion measurements.

The need for simple and robust schemes for the analysis of ligand-protein binding has resulted in the development of diffusion-based NMR techniques that can be used to assay binding in protein solutions containing a mixture of several ligands. As a means of gaining spectral selectivity in NMR diffusion measurements, a simple experiment, the gradient modified spin-echo (GOSE), has been developed to reject the resonances of coupled spins and detect only the singlets in the (1)H NMR spectrum. This is accomplished by first using a spin echo to null the resonances of the coupled spins. Following the spin echo, the singlet magnetization is flipped out of the transverse plane and a dephasing gradient is applied to reduce the spectral artifacts resulting from incomplete cancellation of the J-coupled resonances. The resulting modular sequence is combined here with the BPPSTE pulse sequence; however, it could be easily incorporated into any pulse sequence where additional spectral selectivity is desired. Results obtained with the GOSE-BPPSTE pulse sequence are compared with those obtained with the BPPSTE and CPMG-BPPSTE experiments for a mixture containing the ligands resorcinol and tryptophan in a solution of human serum albumin.

Albumins↗
PubMed2001

Differences in conformational properties of the second intracellular loop (IL2) in 5HT(2C) receptors modified by RNA editing can account for G protein coupling efficiency.

Adenosine-to-inosine RNA editing events that have been demonstrated for 5HT (2C) receptors resulted in alterations of the amino acid sequence at positions 156, 158 and 160 in the intracellular loop 2 (IL2) region. The edited receptor isoforms were shown to have reduced basal activity, but similar maximum responses to agonist binding. To identify the molecular mechanism of these pharmacological effects of editing we explored the conformational properties of the edited IL2 in comparison with the wild type. The results from conformational studies of the IL2 isoforms, using biased Monte Carlo simulations with an implicit solvent model based on a screened Coulomb potential, show that the compared loops differ in their preferred spatial orientations as a result of differences in the conformational space that is accessible to them by energy criteria. For the IL2 of the unedited (5HT (2C-INI) ) receptor, the preference for structures oriented towards the 7TM bundle is larger than for the 5HT (2C-VGV) edited receptor. This difference in preferred orientation can affect the association of IL2 with other intracellular loop domains involved in G protein coupling and hence the coupling efficiency. The results illustrate the high sensitivity of the system to small changes in the interaction surface presented to other intracellular loops, and/or the G protein.

Amino Acid Sequence↗
PubMedDate not supplied

Participatory learning in continuing nursing education: Soviet edition of a public health and medicine trivia game.

The challenge in designing professional continuing education programs lies in balancing the need to provide a new knowledge base with the need to engage the interest of the adult learner. This article reports on the use and evaluation of an experiential and innovative educational approach using adult learning techniques in a continuing education program for nurses in a cross-cultural setting.

Cross-Cultural Comparison↗
PubMed1999

Implementation of a national guideline on prophylaxis of venous thromboembolism: a survey of acute services in Scotland. Thromboembolism Prevention Evaluation Study Group.

BACKGROUND: Deep vein thrombosis (DVT) and pulmonary embolism (PE) are major complications for hospital patients in developed countries. In 1995, the Scottish Intercollegiate Guidelines Network (SIGN) published an evidence-based guideline to encourage the appropriate use of prophylaxis for DVT among hospitalised patients at risk. The guideline was widely distributed within the NHS in Scotland; however, it is not clear what actions trusts have taken to implement it. OBJECTIVE: To investigate the type and extent of DVT guideline implementation activities in acute trusts in Scotland. METHOD: A semi-structured telephone interview with senior clinical audit staff in those trusts with acute services in Scotland. RESULTS: Twenty-nine of the 30 trusts approached participated in the survey (97%). A range of responses to the guideline were reported, including development of local protocols (n = 20), audit of DVT prophylaxis (n = 19), patient specific reminders (n = 13) and provision of a specialist DVT adviser (n = 3). Overall, 25 of the trusts had undertaken guideline development and dissemination activities, and 17 were involved in more active guideline implementation strategies. CONCLUSIONS: The majority of acute trusts in Scotland have responded to the SIGN guideline, usually through the development of local protocols. Strategies to implement the guideline or local protocol are less common. Further guidance is needed on this in the next edition of the guideline.

Clinical Protocols↗
PubMed2005

Discovery of new genes and deletion editing in Physarum mitochondria enabled by a novel algorithm for finding edited mRNAs.

Gene finding is complicated in organisms that exhibit insertional RNA editing. Here, we demonstrate how our new algorithm Predictor of Insertional Editing (PIE) can be used to locate genes whose mRNAs are subjected to multiple frameshifting events, and extend the algorithm to include probabilistic predictions for sites of nucleotide insertion; this feature is particularly useful when designing primers for sequencing edited RNAs. Applying this algorithm, we successfully identified the nad2, nad4L, nad6 and atp8 genes within the mitochondrial genome of Physarum polycephalum, which had gone undetected by existing programs. Characterization of their mRNA products led to the unanticipated discovery of nucleotide deletion editing in Physarum. The deletion event, which results in the removal of three adjacent A residues, was confirmed by primer extension sequencing of total RNA. This finding is remarkable in that it comprises the first known instance of nucleotide deletion in this organelle, to be contrasted with nearly 500 sites of single and dinucleotide addition in characterized mitochondrial RNAs. Statistical analysis of this larger pool of editing sites indicates that there are significant biases in the 2 nt immediately upstream of editing sites, including a reduced incidence of nucleotide repeats, in addition to the previously identified purine-U bias.

Algorithms↗
PubMed1999

Editing of chemical exchange-relayed NOEs in NMR experiments for the observation of protein-water interactions.

An experimental approach for the editing of exchange-relayed NOEs in water-selective NOE experiments is presented. The proposed pulse sequence is based on the application during the NOE mixing time of continuous wave irradiation, which saturates resonances of relaying labile protons in slow chemical exchange with water. The technique can efficiently reduce the contributions of exchange-relayed NOE peaks that often crowd the water-selective NOE spectra and hide direct intermolecular NOEs between water and protein protons. The present approach opens new opportunities for the characterization of hydration by NMR, even in the proximity of polar labile groups.

Macromolecular Substances↗
PubMed1987

A microprocessor system for the digital synthesis of pulsed and continuous discharges of electric fish (or animal vocalizations).

Traditionally, the sensitivity of electric fish to electric stimuli has been investigated using a variety of electronically generated signal functions, for example sine, square, and sawtooth waves (both continuous and pulsed). None of these resemble the species- or sex-specific electric organ discharges (EODs) of fish. Therefore, EODs recorded on magnetic tape were used in open-loop playback experiments. However, as shown in the present paper, the waveforms of EODs reproduced from magnetic tape are distorted, and cannot be manipulated with speed and accuracy as to frequency or pulse repetition rate by feedback from the experiment. Good EOD imitations are generated by our microprocessor-based system for the digital synthesis of EODs which is controlled by a small 'personal computer'. Digitized EOD samples edited by computer are output by the fast digital-to-analogue converter of the microprocessor system. This system was devised for the synthesis of pulse-type (discontinuous) and wave type (continuous) EODs with continuous, on-line frequency and amplitude control. The rate of digital synthesis is 500 kHz in pulse-type EODs, and 250-500 kHz in wave type EODs at 0.06-0.24 Hz frequency resolution, depending on the repetition frequency of the synthesized wave EOD. The present paper describes the steps in EOD synthesis, and indicates some applications which benefit from the playback of high-fidelity imitations of natural EODs at amplitudes and frequencies selected by the experimenter, or automatically controlled by feedback from the experiment in closed-loop applications.

Analog-Digital Conversion↗
PubMed2026

Single-cell mapping of regulatory DNA-protein interactions.

Gene expression is controlled by transcription factors (TFs), whose genome binding is shaped by chromatin accessibility and histone modifications, yet mapping these interactions, particularly those with weak affinity or a transient nature, in single cells remains technically challenging. To address this gap, we developed docking and deamination followed by sequencing (D&D-seq), a single-cell immuno-tethering technology for profiling DNA-protein interactions. D&D-seq couples an antibody-binding nanobody to a cytosine base editor, a combination that enables detection of weak or transient factor binding through targeted cytosine-to-uracil editing at protein-bound genomic sites. This approach is compatible with standard single-cell multi-omic workflows and therefore allows integrated analyses of gene regulation. Using assay for transposase-accessible chromatin using sequencing (ATAC-seq) and single-cell ATAC-seq (scATAC-seq), we assessed chromatin accessibility as a functional readout of TF activity, and by coupling D&D-seq with whole-genome sequencing, we captured CTCF binding in both active and inactive chromatin compartments.

Animals↗
PubMed2003

Online radiology appropriateness survey: results and conclusions from an academic internal medicine residency.

RATIONALE AND OBJECTIVES: This study was performed to evaluate the ability of medical trainees to choose appropriate diagnostic imaging studies for patients with various clinical indications. MATERIALS AND METHODS: Twelve clinical scenarios were excerpted from the 2000 edition of the American College of Radiology appropriateness criteria and arranged in multiple-choice question format. Summary answers based on the criteria were written. The questionnaire and answer key were placed online and linked; the answer key was viewable only after all 12 answers were submitted by the trainee. An invitation to participate in the online survey was forwarded to medical house staff. RESULTS: Sixty-five (43.3%) of 150 potential respondents completed the survey. The results were tabulated for all respondents and separately for each postgraduate-year class. Fewer than 50% of the respondents correctly answered more than half of the 12 questions. The average number of questions answered correctly by 1st-year residents was 7.02; by 2nd-year residents, 7.5; and by 3rd-year residents, 7.9. CONCLUSION: Medical house staff are not adequately prepared to choose appropriate imaging examinations for specific indications. Improvements in education could prevent inappropriate use of radiology resources. Imaging centers might want to consider developing online catalogs to assist clinicians in choosing appropriate imaging tests.

Data Collection↗
PubMed2006

DFT analysis of co-alkyl and co-adenosyl vibrational modes in B12-cofactors.

Density functional theory (DFT)-based normal mode calculations have been carried out on models for B12-cofactors to assign reported isotope-edited resonance Raman spectra, which isolate vibrations of the organo-Co group. Interpretation is straightforward for alkyl-Co derivatives, which display prominent Co-C stretching vibrational bands. DFT correctly reproduces Co-C distances and frequencies for the methyl and ethyl derivatives. However, spectra are complex for adenosyl derivatives, due to mixing of Co-C stretching with a ribose deformation coordinate and to activation of modes involving Co-C-C bending and Co-adenosyl torsion. Despite this complexity, the computed spectra provide a satisfactory re-assignment of the experimental data. Reported trends in adenosyl-cobalamin spectra upon binding to the methylmalonyl CoA mutase enzyme, as well as on subsequent binding of substrates and inhibitors, provide support for an activation mechanism involving substrate-induced deformation of the adenosyl ligand.

Cobamides↗
PubMed1997

FPC: a system for building contigs from restriction fingerprinted clones.

MOTIVATION: To meet the demands of large-scale sequencing, thousands of clones must be fingerprinted and assembled into contigs. To determine the order of clones, a typical experiment is to digest the clones with one or more restriction enzymes and measure the resulting fragments. The probability of two clones overlapping is based on the similarity of their fragments. A contig contains two or more overlapping clones and a minimal tiling path of clones is selected to be sequenced. Interactive software with algorithmic support is necessary to assemble the clones into contigs quickly. RESULTS: FPC (fingerprinted contigs) is an interactive program for building contigs from restriction fingerprinted clones. FPC uses an algorithm to cluster clones into contigs based on their probability of coincidence score. For each contig, it builds a consensus band (CB) map which is similar to a restriction map; but it does not try to resolve all the errors. The CB map is used to assign coordinates to the clones based on their alignment to the map and to provide a detailed visualization of the clone overlap. FPC has editing facilities for the user to refine the coordinates and to remove poorly fingerprinted clones. Functions are available for updating an FPC database with new clones. Contigs can easily be merged, split or deleted. Markers can be added to clones and are displayed with the appropriate contig. Sequence-ready clones can be selected and their sequencing status displayed. As such, FPC is an integrated program for the assembly of sequence-ready clones for large-scale sequencing projects.

Algorithms↗
PubMed1992

Major depressive disorder and dysthymia in young adolescents.

A two-stage epidemiologic study conducted between 1986 and 1988 in the southeastern United States investigated the frequency of major depressive disorder and dysthymia in 12-14 year olds. In stage one, the Center for Epidemiologic Studies Depression Scale, a life event schedule, and a family cohesion scale were administered to a community sample of 3,283 adolescents. In stage two, 488 mother-child pairs were interviewed utilizing the Schedule for Schizophrenia and Affective Disorders in School Age Children. Although mean Center for Epidemiologic Studies Depression Scale scores were significantly higher in females (25.60) than in males (19.50), prevalence estimates based on a summary of mother and child symptom reports for Diagnostic and Statistical Manual of Mental Disorders, Third Edition, major depressive disorder were similar: 9.04% in males and 8.90% in females. The prevalences of dysthymia were 7.98% in males and 5.00% in females. Previous investigations have reported lower rates and a female preponderance of major depression. Disagreement between mothers and children regarding the presence of symptoms may explain this contradiction. Significant odds ratios were found between major depression and not living with both natural parents (odds ratio (OR) = 3.89), undesirable life events (OR = 1.09), and perceived family cohesion (OR = 0.96). Not living with both natural parents (OR = 14.67) and socioeconomic status (OR = 0.44) were significant correlates of dysthymia.

Adolescent↗
PubMed2001

Magnetic space-group types.

The interpretation of Opechowski-Guccione symbols for magnetic space-group types is based on coordinate triplets given in the now superceded International Tables for X-ray Crystallography [(1952), Vol. 1, edited by N. F. M. Henry & K. Lonsdale. Birmingham: Kynoch Press]. Changes to coordinate triplets in International Tables for Crystallography [(1983), Vol. A, edited by Th. Hahn. Dordrecht: Kluwer Academic Publishers] lead to misinterpretations of these symbols. A list is provided here of Opechowski-Guccione symbols for the 1651 magnetic space-group types with their original definitions given independent of International Tables.

Journal Article↗
PubMedDate not supplied

Integration of a multimedia teaching and reference database in a PACS environment.

In one radiology department, a computerized authoring and editing environment was developed and integrated with the picture archiving and communication systems (PACS) for creation of image-based electronic teaching files to replace a collection of printed film images. This multimedia database and authoring environment allows physicians to create reference databases for teaching and research directly from clinical cases being reviewed on PACS diagnostic workstations. The database engine allows users to generate stand-alone CD-ROMs (compact disks, read-only memory) and World Wide Web-based teaching files. The system is fully compliant with the Digital Imaging and Communications in Medicine (DICOM) standard and supports a large number of standard multimedia image file formats. The focus of the development was on convenience and ease of use of a generic system adaptable to all users. The software was integrated on the PACS workstations to allow users to add new cases to the database at any time and anywhere in the department. A pilot system was implemented in clinical operation, with a central server and several client units.

CD-ROM↗
PubMed2001

Factor index score patterns in the WAIS-III standardization sample.

Representative profile subtypes, based on factor index scores, were examined in the standardization sample of the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III). Two-stage cluster analysis identified five reliable subtypes. Three clusters were differentiated primarily by level of performance across all factor index scores (ranging from below average, to average, to above average). The other two clusters were characterized by distinct patterns of performance, with relative efficacy on the Processing Speed index being the most prominent distinction (ranging from a relative weakness to a relative strength). The clusters did not differ significantly in age, but ethnicity and income covaried directly with level of WAIS-III performance, whereas gender affected differential patterns of performance. Furthermore, education and memory were associated primarily with level and, to a relatively minor degree, pattern of WAIS-III performance. Implications for clinical practice are discussed.

Chi-Square Distribution↗
PubMedDate not supplied

Constitutional protection against discrimination of homosexuals.

A brief review of equality for homosexuals prior to 1983 is presented followed by the introduction and explanation of the relevant section of the revised edition of the Dutch Constitution (enacted in 1983). The possible impact of this section on the abolishment of discrimination based on sex and sexual orientation is discussed.

Civil Rights↗