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PubMed2002

[Study on the editing sites of the coxII gene transcripts of rice mitochondria].

The term RNA editing is generally used to describe those molecular processes in which the information content is altered in an RNA molecule. This process is not limited to mRNA since alterations of non-informational RNA have also been found. RNA editing exists extensively in the higher plant mitochondria, and is the necessary step for forming functional proteins. In this paper, the research materials are the gametopthyte male sterility line (A), maintainer line (B) and F1 hybrid (F1) of HL-type CMS. 15 editing sites are found in the transcripts of coxII by comparing cDNAs and DNAs sequences. A,B and F1 have same Editing sites. When editing occurs at the first or second position of codons, the encoded amino acid is likely to be altered. As a result, the conservation of the predicted protein is improved as compared with other organisms.

Base Sequence↗
PubMed1996

Report on the RCDS-CDHSRU workshop on developing clinical guidelines/standards of practice.

Investigators from the Community Dental Health Services Research Unit (CDHSRU) held a workshop to test a model for developing clinical guidelines/standards of practice, which are required under the Regulated Health Professions Legislation. Forty-two individuals from Ontario and Canada, including dentists, representatives of the public, and professionals, participated in the three-day workshop, held under the auspices of the quality assurance committee of the Royal College of Dental Surgeons of Ontario (RCDS). Through direct experience, workshop participants sought to learn each of the steps, as defined by the literature, involved in clinical guideline development. Ultimately, they hoped to recommend steps for RCDS to follow in developing standards of practice. To ensure that a realistic and valid model emerged from the workshop, a real topic, namely the management of smooth surface enamel lesions in permanent teeth, was used to develop and test clinical guidelines. Prior to the workshop, participants were sent literature on one of five aspects of the topic, as well as papers describing the methodology of critically appraising the literature, and partially-completed templates outlining the basic steps to be followed. During the first evening and first morning of the workshop, participants listened to presentations on the development of clinical guidelines, the prevalence of smooth surface lesions, the role of economics in guideline development, and the necessary considerations in writing clinical guidelines. Under the leadership of trained facilitators, they then worked in small groups to write evidence-based recommendations and report them to the other workshop participants for feedback. Using this feedback, they returned to their groups to revise their recommendations and work on the workshop's overall recommendations to the RCDS. The day concluded in the evening, when the workshop facilitators and coordinators met to edit the groups' recommendations into a consistent format for presentation to all participants. On the second morning, the participants attended a plenary session to review the evidence-based recommendations developed by the groups, as well as their overall recommendations on the steps to be followed by the RCDS. Ultimately, workshop participants partially completed the templates and developed preliminary evidence-based recommendations on the management of enamel smooth-surface caries. Based on their experiences, they recommended a seven-step process for the future development of clinical practice guidelines/standards of practice in Ontario. These steps are recommendations only, and are not RCDS policy.

Canada↗
PubMed1997

RNA editing in kinetoplastid protozoa.

Mitochondrial transcripts in kinetoplastids undergo remarkable posttranscriptional editing by uridylate insertion and deletion. The often dramatic remodeling of pre-mRNA sequences is directed by small guide RNAs (gRNAs) to produce mature mRNAs. In vitro analyses of editing have been used to determine the mechanism of editing and show that editing occurs by a series of enzyme-catalyzed steps. They also show that chimeric gRNA/mRNA molecules are not editing intermediates as proposed but are aberrant end products of editing. The complexes and molecules that catalyze editing are now being identified and characterized. The origin of editing, its developmental regulation which helps control the switching between terminal respiratory systems during the life cycle of trypanosomes, and other areas for future study are discussed.

Animals↗
PubMed2001

Primary transcripts of ndhD of Liliaceae and Aloaceae require editing of the start and 20th codons.

About 350 nucleotide sequences around the start codon of the plastid ndhD gene were determined in six species to investigate the requirement of C to U editing of the cryptic start codons. The comparison with other sequences in databanks showed that, in contrast to grasses and similarly to dicots, Liliaceae and Aloaceae require editing of the primary transcript to generate the AUG start codon. Primary transcripts of Liliaceae and Aloaceae also show a new editing site at the 59th nucleotide, which has not been described in other plants. In some cases, transcripts showed partial editing which suggests that the synthesis of the protein may be controlled at the level of transcript processing.

Amino Acid Sequence↗
PubMed1994

Complementation of apolipoprotein B mRNA editing by human liver accompanied by secretion of apolipoprotein B48.

Mammalian small intestine secretes a truncated apolipoprotein B (apoB48) species as a result of tissue-specific post-transcriptional RNA editing. The human liver, by contrast, contains only unedited apoB mRNA and secretes only apoB100. We have recently isolated a cDNA clone from rat small intestine which encodes an apoB mRNA editing protein, REPR (Teng, B., Burant, C.F., and Davidson, N.O. (1993) Science 260, 1816-1819). The current study demonstrates that homogenates of Xenopus oocytes expressing REPR confer editing ability upon S100 extracts prepared from human liver when tested on a synthetic apoB RNA template in vitro. Transfection of REPR into HepG2 cells resulted in editing of endogenous apoB mRNA and the appearance of an apoB48-like protein in the media. Extracts prepared from these transfected cells edit mammalian apoB RNA templates when incubated alone and with enhanced efficiency in the presence of chicken intestinal S100 extracts. The results suggest that human liver expresses factor(s) which are critical to apoB mRNA editing and which allow functional complementation of REPR in vivo.

APOBEC-1 Deaminase↗
PubMed2006

Recollection rejection of false narrative statements.

Our research was focused on a false-memory editing operation that is posited in fuzzy-trace theory-recollection rejection. The main objectives were (a) to extend model-based measurement of this operation to a narrative task that ought to ensure high levels of recollection rejection and (b) to study five manipulations that ought to influence recollection rejection by affecting the accessibility of verbatim traces of narrative statements: recency of narrative presentation, narrative repetition, type of false-memory item, testing delay, and repeated testing. The results showed that the narrative task did indeed yield high levels of recollection, with an estimated 49% of gist-consistent distractors being rejected in this way on initial memory tests. Consistent with current theoretical conceptions of false-memory editing, the results also showed that recollection rejection increased as a function of manipulations that should enhance the accessibility of verbatim traces of narrative statements, with repeated testing delivering especially large increases in verbatim accessibility.

Attention↗
PubMedDate not supplied

Treatment with buspirone in a patient with autism.

This study evaluates the safety and efficacy of buspirone hydrochloride for the treatment of a patient with autism and hyperactivity disorder and determines the effect of buspirone on the number of performance tasks completed by the patient at school. A 3-week, double-blind, placebo-controlled crossover study was performed in a private physician, office-based practice. A child with autism, which was diagnosed by Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised, criteria, was studied. The child received placebo for 3 weeks and buspirone for 3 weeks; there was a 1-week interval between the 2 treatments. The outcome was measured by using Conners abbreviated parent and teacher questionnaires and by determining the number of daily performance tasks completed by the child at school. Statistical analysis was performed by linear models and standard F tests. Buspirone was found to be safe and efficacious, without side effects, for decreasing hyperactivity and increasing completed performance tasks. The beneficial effects of buspirone in helping this patient with autism in his natural daily settings suggest that buspirone may be an alternative to neuroleptic agents in the medical therapy of autism; further study in other patients is needed.

Anti-Anxiety Agents↗
PubMed2001

Exposure to violence: psychological and academic correlates in child witnesses.

BACKGROUND: Inner-city children are frequently exposed to violence; however, there are few data regarding the psychological and academic correlates of such exposure in young children at school entry. OBJECTIVES: To document exposure to violence in inner-city children aged 7 years; assess their feelings of distress; and evaluate the relationships of exposure to violence with school performance, behavior, and self-esteem. SETTING: A study center in an inner-city hospital. PARTICIPANTS: One hundred nineteen inner-city children evaluated at age 7 years; 119 caregivers (biological and foster). DESIGN: As part of a longitudinal study, children were administered the following by a masked examiner: Things I Have Seen and Heard (TISH) to assess exposure to violence; Levonn, a cartoon-based interview for assessing children's distress symptoms; and the Culture-Free Self-Esteem Inventory, Second Edition. School performance was assessed by school reports and child behavior by the Child Behavior Checklist (CBCL), the Parent Report Form, and the Teacher Report Form. Caregivers for children were administered the parent report version of the Checklist of Children's Distress Symptoms (CCDS-PRV) as well as the CBCL Parent Report Form. MAIN OUTCOME MEASURES: Exposure to violence (TISH); feelings of distress (Levonn); school performance; behavior (CBCL Parent Report Form and CBCL Teacher Report Form); and self-esteem (Culture-Free Self-Esteem Inventory). RESULTS: We found that these children were frequently exposed to violence. For example, 75% had heard gun shots, 60% had seen drug deals, 18% had seen a dead body outside, and 10% had seen a shooting or stabbing in the home (TISH). Many showed signs of depression and anxiety; eg, 61% worried some or a lot of the time that they might get killed or die and 19% sometimes wished they were dead (Levonn). Higher exposure to violence (TISH Total Violence score) was correlated with higher Levonn composite scores for depression and anxiety and with lower self-esteem (P< or =.04), and was also associated with lower grade point average and more days of school absence (P< or =.02). Caregiver assessment of child anxiety correlated poorly with child report of anxiety (P =.58). CONCLUSIONS: Young inner-city children have a high exposure to violence by age 7 years; many show signs of distress that frequently are not recognized by caregivers. Further, higher exposure to violence in children correlates with poorer performance in school, symptoms of anxiety and depression, and lower self-esteem.

Anxiety Disorders↗
PubMed1992

Silent mitochondrial and active nuclear genes for subunit 2 of cytochrome c oxidase (cox2) in soybean: evidence for RNA-mediated gene transfer.

In most plants and other eukaryotes investigated, the mitochondrial genome carries the gene encoding subunit 2 of cytochrome c oxidase (cox2). In this paper, we show that the previously reported mitochondrial cox2 of soybean is actually silent, and that there is an expressed, single-copy, nucleus-encoded cox2. Molecular cloning and sequence analysis of cox2 cDNA and genomic clones show that the soybean nuclear gene encodes an N-terminal extension that resembles a signal sequence for mitochondrial import and whose coding sequence is separated by an intron from that corresponding to mtDNA-encoded cox2. Comparison of soybean mitochondrial and nuclear cox2 sequences clearly indicates that in an ancestor of soybean, cox2 was transferred from the mitochondrion to the nucleus via a C-to-U edited RNA intermediate.

Amino Acid Sequence↗
PubMed2006

Human brain evolution and the "Neuroevolutionary Time-depth Principle:" Implications for the Reclassification of fear-circuitry-related traits in DSM-V and for studying resilience to warzone-related posttraumatic stress disorder.

The DSM-III, DSM-IV, DSM-IV-TR and ICD-10 have judiciously minimized discussion of etiologies to distance clinical psychiatry from Freudian psychoanalysis. With this goal mostly achieved, discussion of etiological factors should be reintroduced into the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V). A research agenda for the DSM-V advocated the "development of a pathophysiologically based classification system". The author critically reviews the neuroevolutionary literature on stress-induced and fear circuitry disorders and related amygdala-driven, species-atypical fear behaviors of clinical severity in adult humans. Over 30 empirically testable/falsifiable predictions are presented. It is noted that in DSM-IV-TR and ICD-10, the classification of stress and fear circuitry disorders is neither mode-of-acquisition-based nor brain-evolution-based. For example, snake phobia (innate) and dog phobia (overconsolidational) are clustered together. Similarly, research on blood-injection-injury-type-specific phobia clusters two fears different in their innateness: 1) an arguably ontogenetic memory-trace-overconsolidation-based fear (hospital phobia) and 2) a hardwired (innate) fear of the sight of one's blood or a sharp object penetrating one's skin. Genetic architecture-charting of fear-circuitry-related traits has been challenging. Various, non-phenotype-based architectures can serve as targets for research. In this article, the author will propose one such alternative genetic architecture. This article was inspired by the following: A) Nesse's "Smoke-Detector Principle", B) the increasing suspicion that the "smooth" rather than "lumpy" distribution of complex psychiatric phenotypes (including fear-circuitry disorders) may in some cases be accounted for by oligogenic (and not necessarily polygenic) transmission, and C) insights from the initial sequence of the chimpanzee genome and comparison with the human genome by the Chimpanzee Sequencing and Analysis Consortium published in late 2005. Neuroevolutionary insights relevant to fear circuitry symptoms that primarily emerge overconsolidationally (especially Combat related Posttraumatic Stress Disorder) are presented. Also introduced is a human-evolution-based principle for clustering innate fear traits. The "Neuroevolutionary Time-depth Principle" of innate fears proposed in this article may be useful in the development of a neuroevolution-based taxonomic re-clustering of stress-triggered and fear-circuitry disorders in DSM-V. Four broad clusters of evolved fear circuits are proposed based on their time-depths: 1) Mesozoic (mammalian-wide) circuits hardwired by wild-type alleles driven to fixation by Mesozoic selective sweeps; 2) Cenozoic (simian-wide) circuits relevant to many specific phobias; 3) mid Paleolithic and upper Paleolithic (Homo sapiens-specific) circuits (arguably resulting mostly from mate-choice-driven stabilizing selection); 4) Neolithic circuits (arguably mostly related to stabilizing selection driven by gene-culture co-evolution). More importantly, the author presents evolutionary perspectives on warzone-related PTSD, Combat-Stress Reaction, Combat-related Stress, Operational-Stress, and other deployment-stress-induced symptoms. The Neuroevolutionary Time-depth Principle presented in this article may help explain the dissimilar stress-resilience levels following different types of acute threat to survival of oneself or one's progency (aka DSM-III and DSM-V PTSD Criterion-A events). PTSD rates following exposure to lethal inter-group violence (combat, warzone exposure or intentionally caused disasters such as terrorism) are usually 5-10 times higher than rates following large-scale natural disasters such as forest fires, floods, hurricanes, volcanic eruptions, and earthquakes. The author predicts that both intentionally-caused large-scale bioevent-disasters, as well as natural bioevents such as SARS and avian flu pandemics will be an exception and are likely to be followed by PTSD rates approaching those that follow warzone exposure. During bioevents, Amygdala-driven and locus-coeruleus-driven epidemic pseudosomatic symptoms may be an order of magnitude more common than infection-caused cytokine-driven symptoms. Implications for the red cross and FEMA are discussed. It is also argued that hospital phobia as well as dog phobia, bird phobia and bat phobia require re-taxonomization in DSM-V in a new "overconsolidational disorders" category anchored around PTSD. The overconsolidational spectrum category may be conceptualized as straddling the fear circuitry spectrum disorders and the affective spectrum disorders categories, and may be a category for which Pitman's secondary prevention propranolol regimen may be specifically indicated as a "morning after pill" intervention. Predictions are presented regarding obsessive-compulsive disorder (OCD) (e.g., female-pattern hoarding vs. male-pattern hoarding) and "culture-bound" acute anxiety symptoms (taijin-kyofusho, koro, shuk yang, shook yong, suo yang, rok-joo, jinjinia-bemar, karoshi, gwarosa, Voodoo death). Also discussed are insights relevant to pseudoneurological symptoms and to the forthcoming Dissociative-Conversive disorders category in DSM-V, including what the author terms fright-triggered acute pseudo-localized symptoms (i.e., pseudoparalysis, pseudocerebellar imbalance, psychogenic blindness, pseudoseizures, and epidemic sociogenic illness). Speculations based on studies of the human abnormal-spindle-like, microcephaly-associated (ASPM) gene, the microcephaly primary autosomal recessive (MCPH) gene, and the forkhead box p2 (FOXP2) gene are made and incorporated into what is termed "The pre-FOXP2 Hypothesis of Blood-Injection-Injury Phobia." Finally, the author argues for a non-reductionistic fusion of "distal (evolutionary) neurobiology" with clinical "proximal neurobiology," utilizing neurological heuristics. It is noted that the value of re-clustering fear traits based on behavioral ethology, human-phylogenomics-derived endophenotypes and on ontogenomics (gene-environment interactions) can be confirmed or disconfirmed using epidemiological or twin studies and psychiatric genomics.

Animals↗
PubMed2003

New insights into the evolutionary relationships between arenaviruses provided by comparative analysis of small and large segment sequences.

Arenaviruses are rodent-borne negative-stranded bisegmented RNA viruses. Five arenaviruses are etiologic agents of hemorrhagic fever in humans and are potential agents of bioterrorism. They are classified as Biosafety level 4 agents and listed in the category A of the Pathogen Agents edited by the Center for Disease Control and Prevention. To date, evolution and phylogeny of arenaviruses have been based on the analysis of sequences derived from structural genes (small RNA segment) exclusively, due to the lack of sequences available for the large RNA segment. In this study, partial sequences of the polymerase gene were determined for 18 species of arenaviruses and used to investigate phylogenetic relationships. Comparative analysis of topologies obtained from polymerase and structural gene analyses permitted us to determine the evolutionary origin of the major parent of the North American recombinant arenaviruses, and to investigate the role of genetic exchange (reassortment and recombination) in the evolutionary mechanisms driving the evolution of the genus Arenavirus.

Arenaviruses, New World↗
PubMed1983

Effects of segment and pause manipulations on the identification of treated stutterers.

This study examined the hypothesis that reading rate affects the identification of treated stutterers. Thirty-two pairs of recorded speech samples, in which one member of the pair was a treated stutterer and the other was a nonstutterer, were available from previous research. Listeners had been able to distinguish readily between the members of these pairs. For each pair of samples, the durations of the treated stutterer's segments and pauses were adjusted to match those of the nonstutterer as closely as possible by means of a computer-based waveform editor. A test tape was prepared that included the 32 original pairs of stimuli, the 32 edited pairs, and 64 pairs of foils. Listeners were required to indicate which member of each pair was the treated stutterer. Analysis of the responses indicated that the listeners' ability to distinguish between talkers was significantly reduced for the edited stimulus pairs. The results imply that the rate used by treated stutterers must be critically evaluated if the goal of therapy is the production of perceptually "normal" speech.

Female↗
PubMed2003

Genomic organization of Trypanosoma brucei kinetoplast DNA minicircles.

The sequences of seven new Trypanosoma brucei kinetoplast DNA minicircles were obtained. A detailed comparative analysis of these sequences and those of the 18 complete kDNA minicircle sequences from T. brucei available in the database was performed. These 25 different minicircles contain 86 putative gRNA genes. The number of gRNA genes per minicircle varies from 2 to 5. In most cases, the genes are located between short imperfect inverted repeats, but in several minicircles there are inverted repeat cassettes that did not contain identifiable gRNA genes. Five minicircles contain single gRNA genes not surrounded by identifiable repeats. Two pairs of closely related minicircles may have recently evolved from common ancestors: KTMH1 and KTMH3 contained the same gRNA genes in the same order, whereas KTCSGRA and KTCSGRB contained two gRNA genes in the same order and one gRNA gene specific to each. All minicircles could be classified into two classes on the basis of a short substitution within the highly conserved region, but the minicircles in these two classes did not appear to differ in terms of gRNA content or gene organization. A number of redundant gRNAs containing identical editing information but different sequences were present. The alignments of the predicted gRNAs with the edited mRNA sequences varied from a perfect alignment without gaps to alignments with multiple mismatches. Multiple gRNAs overlapped with upstream gRNAs, but in no case was a complete set of overlapping gRNAs covering an entire editing domain obtained. We estimate that a minimum set of approximately 65 additional gRNAs would be required for complete overlapping sets. This analysis should provide a basis for detailed studies of the evolution and role in RNA editing of kDNA minicircles in this species.

Animals↗
PubMed1981

Research criteria for male erectile failure.

Although the spectrum of psychosexual disorders is rather broad, there is a specific subgroup of sexual function disorders which has recently received wide attention due to the increased treatment success reported with the use of primarily behavioral means. Classification in this area, however, has been quite variable making replication of studies quite difficult. Although this is somewhat improved in the new psychiatric nomenclature DSM III, that nomenclature is still not physiologically based and does not allow the specificity necessary for replication of studies for research. We present here a nosology for the sexual function disorders based on physiology and with the capability of specificity necessary for replication. It is adaptable to the current edition of DSM III.

Adult↗
PubMed2004

Editing anti-DNA B cells by Vlambdax.

Receptor editing is performed by replacement of Vkappa genes that contribute to autoreactivity. In addition, the Ckappa locus can be deleted by Vkappa rearrangement to intronic or 3' of Ckappa RS sequences (also referred to as kappa deletion elements). B cells that delete the Ckappa can then express lambda light chains. However, the lambda locus, either of man or mouse, does not allow V gene replacement. Nor does it appear to be deleted. Therefore, editing of autoreactive lambda B cells may require alternative pathways. We have found that in anti-DNA heavy chain transgenic mice (tgs) VH3H9/56R, B cells that express anti-DNA receptors comprised of lambda1 in association with an anti-DNA heavy chain often coexpress a kappa chain that prevents DNA binding. We speculate that such isotypically included cells may have low anti-DNA receptor densities, a feature that may lead to self-tolerance. Here we describe a mechanism of preventing DNA binding by expression of a rarely used member of the Vlambda family, Vlambdax. The lambdax B cells of the tgs also express CD25 and may represent B cells that have exhausted light chain editing possibilities.

Animals↗
PubMed2001

Heterologous, splicing-dependent RNA editing in chloroplasts: allotetraploidy provides trans-factors.

RNA editing is unique among post-transcriptional processes in plastids, as it exhibits extraordinary phylogenetic dynamics leading to species-specific editing site patterns. The evolutionary loss of a site is considered to entail the loss of the corresponding nuclear-encoded site-specific factor, which prevents the editing of foreign, i.e. heterologous, sites. We investigated the editing of short 'spliced' and 'unspliced' ndhA gene fragments from spinach in Nicotiana tabacum (tobacco) in vivo using biolistic transformation. Surprisingly, it turned out that the spinach site is edited in the heterologous nuclear background. Furthermore, only exon-exon fusions were edited, whereas intron-containing messages remained unprocessed. A homologue of the spinach site was found to be present and edited in Nicotiana tomentosiformis, representing the paternal parent, but absent from Nicotiana sylvestris, representing the maternal parent of tobacco. Our data show that: (i) the cis-determinants for ndhA editing are split by an intron; (ii) the editing capacity cannot be deduced from editing sites; and (iii) allopolyploidization can increase the editing capacity, which implies that it can influence speciation processes in evolution.

Base Sequence↗
PubMed1982

Automation of the computer handling of gel reading data produced by the shotgun method of DNA sequencing.

This paper describes a computer method for handling gel reading data produced by the shotgun method of DNA sequencing. The method greatly reduces the time the sequencer needs to spend checking and editing his data and yet it produces a consensus sequence for which the accuracy of determination of every base can be clearly shown. The program can take a batch of new gel readings, screen them against vector sequences removing any that match, and then compare and align all the sequences to produce a final consensus. No information is lost in this process as alignments are achieved by making only insertions and because all the individual gel readings are added to a database from which they can be retrieved and displayed lined up one above the other. This allows the user to check on the alignments achieved by the program and if necessary change them. As each gel reading is added to the database the consensus is automatically updated accordingly and used for the next comparisons. This is a much faster process than comparing each new gel against every individual gel in the database.

Autoanalysis↗