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PubMed1990

Editing of the wheat coxIII transcript: evidence for twelve C to U and one U to C conversions and for sequence similarities around editing sites.

The complete cDNA sequence corresponding to the wheat coxIII gene transcript (coding for subunit 3 of cytochrome oxidase) has been determined by a method involving cDNA synthesis using specific oligonucleotides as primers followed by PCR amplification, cloning and sequencing of the amplification products. In 12 different clones, the same 13 nucleotide modifications have been found as compared to the genomic mitochondrial DNA sequence. Among these modifications, 12 are C----U conversions which change codons identities, thereby increasing the homology between the wheat COXIII protein and the corresponding protein of non-plant organisms. The 13th modification is a silent U----C conversion which seems to be an unfrequent editing eventin plant mitochondria. Homologies can be found between sequences surrounding editing sites in the coxIII transcript and in other wheat mitochondrial transcripts. The presence of such homology suggests that these sequences could base-pair with a common RNA molecule which might be involved in editing site recognition.

Amino Acid Sequence↗

PubMed2004

In vitro characterization of a tRNA editing activity in the mitochondria of Spizellomyces punctatus, a Chytridiomycete fungus.

In the chytridiomycete fungus, Spizellomyces punctatus, all eight of the mitochondrially encoded tRNAs are predicted to have one or more base pair mismatches at the first three positions of their aminoacyl acceptor stems. These tRNAs are edited post-transcriptionally by replacement of the 5'-nucleotide in each mismatched pair with a nucleotide that can form a standard Watson-Crick base pair with its counterpart in the 3'-half of the stem. The type of mitochondrial tRNA editing found in S. punctatus also occurs in Acanthamoeba castellanii, a distantly related amoeboid protist. Using an S. punctatus mitochondrial extract, we have developed an in vitro assay of tRNA editing in which nucleotides are incorporated into various tRNA substrates. Experiments employing synthetic transcripts revealed that the S. punctatus tRNA editing activity incorporates nucleotides on the 5'-side of substrate tRNAs, uses the 3'-sequence as a template for incorporation, and adds nucleotides in a 3'-to-5' direction. This activity can add nucleotides to a triphosphorylated 5'-end in the absence of ATP but requires ATP to add nucleotides to a monophosphorylated 5'-end; moreover, it functions independently of the state of tRNA 3' processing. These data parallel results obtained in a previous in vitro study of A. castellanii tRNA editing, suggesting that remarkably similar activities function in the mitochondria of these two organisms. The evolutionary origins of these activities are discussed.

Adenosine Triphosphate↗

PubMed2002

Treatment of erectile dysfunction in patients with Peyronie's disease using sildenafil citrate.

Erectile dysfunction (ED) has frequently been associated with Peyronie's Disease (PD) and may further compromise coitus. This is a retrospective analysis of ED in patients with PD since the release of sildenafil citrate (SC) focusing specifically on our patients' responses to SC. One-hundred seventy six patients with PD were evaluated between April 1998 and May 2001. All patients received a complete medical and sexual history, physical exam, penile duplex ultrasound (PDU, with 30-90 mg of papaverine) to assess penile vascular integrity, plaque dimensions, and erect penile deformity. Based on these findings, appropriate treatment options were offered for their PD and their ED including SC, which was offered to 73 men. Patient response to SC was specifically assessed during patient office interview and via a mailed EDITS (Erectile Dysfunction Inventory of Treatment Satisfaction) questionnaire. Seventy (39.8%) and 104 (59.1%) patients complained of decreased erectile capacity (ie rigidity) occurring before and after the onset of PD, respectively. Only two patients reported no change of erectile capacity. In all, 103 (58.5%) patients complained of significant reduction in sexual function due to diminished rigidity and sought treatment for their ED. Of the ED treatment options available, 73 (70.9%) patients were given a prescription for SC. Forty-eight (75.0%) patients returned the EDITS questionnaire while four of 73 (5.5%) patients did not fill their prescription and five of 73 (6.8%) did not engage in sexual activity following an initial trial of SC due to side effects (flushing, headaches). Based upon the EDITS response, 34 of 48 (70.8%) patients reported that they were either very satisfied or somewhat satisfied, five of 48 (10.4%) patients were neither satisfied nor dissatisfied, and nine of 48 (18.8%) patients were somewhat dissatisfied or very dissatisfied with the effectiveness of SC in enhancing their erectile response. No patient reported worsening of PD deformity or an increase in penile pain. The 30 patients who were not prescribed SC chose the following options to enhance rigidity: eight (7.8%) underwent prosthesis placement, four (3.9%) opted for vacuum constriction device (VCD), four (3.9%) chose intracorporal injections, and 14 (13.6%) used no adjunctive therapy. Erectile dysfunction is a problem associated with PD and all typical treatment options are acceptable. However, to our knowledge, there is no published study reviewing the efficacy of SC in patients with ED associated with PD. There appears to be no contraindication to using SC as being the least invasive and most convenient treatment option for ED with PD. Although the potential risk of coital trauma to the erect penis with PD is present, there is no evidence from this study that erections and coitus enhanced specifically by SC resulted in worsening deformity or progression of the PD. EDITS questionnaire results reveal that SC is an agent that allowed successful coitus in 70.8% of males with PD.

Arteries↗

PubMed1986

Red blood cell antibody identification and confirmation using commercial panels. A computer program for the IBM personal computer.

A menu-driven computer program that utilizes a data base of commercial panels was developed to assist in the identification and confirmation of red blood cell antibodies. A selected panel, along with the corresponding serum reactions, is displayed on the monitor and possible antibody patterns including dosage-dependent patterns are highlighted. A panel interpretation is then printed that includes a list of the possible (nonexcluded) antibodies, a probability level of identification for each possible antibody, and a table of antibody characteristics to aid in the differentiation among the possible antibodies. The panel data base can also be searched for additional red blood cells of specified phenotypes to confirm each suspected antibody. These additional red blood cells may be combined into a temporary panel for computer analysis. The program can also enter, print, edit, and delete any commercial panel from the data base. This computer program has proved to be faster and more accurate than the standard manual method for panel analysis, especially when multiple antibodies are present.

Antibodies↗

PubMedDate not supplied

Development and validation of an instrument to measure physicians' attitudes toward the clinical pharmacist's role.

A scale to measure physicians' attitudes toward clinical pharmacy was developed and validated. Based on physician-clinical pharmacist interactions, statements were written and edited into tentative subscales. A preliminary test resulted in a reduction in the number of items and subscales. The final field test, based on responses from 166 physicians, after factor analysis, yielded 23 items in 5 subscales, with a scale reliability of 0.94. As additional measures of validity, physicians' responses showed significant differences in attitudes between subscales and differences by specialty. Differences also were demonstrated by physician status and age. No differences were shown by amount of exposure to clinical pharmacists. Reliability and validity of the scale have been supported and additional research into the concurrent validity of the scale is suggested.

Age Factors↗

PubMed2005

Crystallization and X-ray diffraction analysis of the Trp/amber editing site of hepatitis delta virus (+)RNA: a case of rational design.

RNA editing by mammalian ADAR1 (Adenosine Deaminase Acting on RNA) is required for the life cycle of the hepatitis delta virus (HDV). Editing extends the single viral open reading frame to yield two protein products of alternate length. ADARs are believed to recognize double-stranded RNA substrates via a ;structure-based' readout mechanism. Crystals of 10-mer duplexes representing the HDV RNA-editing site diffracted to 1.35 A resolution, but suffered from merohedral twinning and averaging of the base registry. Expansion of the construct to include two flanking 3 x 1 internal loops yielded crystals in the primitive tetragonal space group P4(1)2(1)2 or P4(3)2(1)2. X-ray diffraction data were collected to 2.8 A resolution, revealing a unit cell with parameters a = 62.5, c = 63.5 A. The crystallization and X-ray analysis of multiple forms of the HDV RNA-editing substrate, encounters with common RNA crystal-growth defects and a strategy to overcome these problems are reported.

Base Sequence↗

PubMed2026

From Gene Function to Precision Intervention: CRISPR/Cas9 and Stem Cell-Based Strategies as Emerging Disease-Modifying Approaches in PMOS.

Polyendocrine metabolic ovarian syndrome (PMOS) is a complex endocrine-metabolic disorder affecting up to 18% of women worldwide and remains the leading cause of anovulatory infertility. Despite extensive research, current treatments primarily target symptoms, including menstrual irregularities, hyperandrogenism, and metabolic dysfunction, without addressing the underlying molecular and tissue-level disturbances. Advances in multi‑omic profiling have identified disruptions across neuroendocrine, metabolic, inflammatory, and extracellular matrix pathways, alongside genetic susceptibility at loci such as DENND1A, CYP17A1, LHCGR, FSHR, IRS1, and PPARG. However, the functional roles of many variants remain unresolved. CRISPR/Cas9 gene editing enables precise interrogation of these pathways, while stem cell-based platforms, including mesenchymal stem cells (MSCs), exosomes, and gene-edited induced pluripotent stem cells (iPSCs), may serve as complementary platforms for regeneration and disease modeling. Preclinical studies demonstrate that MSCs and their derivatives modulate inflammation, restore ovarian structure, and improve metabolic parameters, while iPSC-based models enable patient-specific investigation of steroidogenic and metabolic abnormalities. Translational challenges remain, including targeted delivery, off-target effects, phenotypic heterogeneity, and regulatory considerations. Integrating CRISPR‑based functional genomics with stem cell research may shift PMOS management from symptom‑focused care to targeted, mechanism‑driven interventions that could modify the course of PMOS (Graphical Abstract).

Humans↗

PubMed1997

[RNA editing].

Explore the source record for details and available documents.

Animals↗

PubMed1995

RNA editing in higher plant mitochondria: analysis of biochemistry and specificity.

RNA editing alters genomically encoded cytidines to uridines posttranscriptionally in higher plant mitochondria. Most of these editing events occur in translated regions and consequently alter the amino acid sequence. In Oenothera berteriana more than 500 editing sites have been detected and the total number of editing sites exceeds 1000 sites in this mitochondrial genome. To identify the components involved in this process we investigated the factors determining the specificity of RNA editing and the apparent conversion of cytidine to uridine residues. The possible biochemical reactions responsible for RNA editing in plant mitochondria are de- or transamination, base substitution and nucleotide replacement. In order to discriminate between these different biochemical mechanisms we followed the fate of the sugar-phosphate backbone by analysing radiolabeled nucleotides after incorporation into high molecular mass RNA. Plant mitochondria were supplied with [alpha-32P]CTP to radiolabel CMP residues in newly synthesized transcripts. Radiolabeled mtRNA was extracted and digested with nuclease P1 to hydrolyse the RNA to monophosphates. The resulting monophosphates were analysed on one- and two-dimensional TLC systems to separate pC from pU. Radiolabeled pU was detected in increasing quantities during the course of incubation. These results suggest that RNA editing in plant mitochondria involves either a deamination or a transglycosylation reaction. The editing product was identified as uridine and not as a hypermodified nucleotide which is recognized as uridine. Similar results have been obtained by incubating in vitro transcribed mRNAs with mitochondrial lysates indicating that RNA editing and transcription is not directly linked in plant mitochondria.(ABSTRACT TRUNCATED AT 250 WORDS)

Biological Evolution↗

PubMed2004

Methods for the analysis of adenosine-to-inosine editing in RNA.

In this work we describe methods for the analysis of RNAs that have been edited by the double-strand RNA-specific adenosine deaminase, ADAR. These RNAs contain inosine residues that can be detected and quantified by a variety of approaches, including base hydrolysis and thin-layer chromatography, reverse transcription polymerase chain reaction, primer extension, and inosine-specific base cleavage. The most common method for the analysis of editing will be described here. This method involves complete hydrolysis of edited RNAs to nucleoside monophosphates, followed by separation of the products using thin-layer chromatography.

Adenosine↗

PubMed1995

The relationships among anxiety, depression, and pain in a geriatric institutionalized sample.

This study sought to determine if depression and/or anxiety is uniquely related to pain after controlling for the strong association between anxiety and depression. Both depression and anxiety were assessed in an elderly institutionalized sample using: (1) research-based diagnoses based on Diagnostic and Statistical Manual-revised 3rd edition (DSM-IIIR) criteria, and (2) evaluations of one's recent affective states using the Profile of Moods States (POMS). Pain was assessed by pain intensity and number of pain complaints. A series of path models indicated that: (1) both research-based anxiety and depression share unique variance with pain, and (2) only POMS anxiety is uniquely related to pain. A path model using both measures of anxiety and depression indicated that only the anxiety measures are significantly related to pain. However, POMS anxiety sustained a significantly greater relationship with pain than did research-based anxiety.

Age Factors↗

PubMed1996

RNA editing is required for efficient excision of tRNA(Phe) from precursors in plant mitochondria.

RNA editing corrects a 4C-A69 mismatch to a conventional 4T-A69 Watson-Crick base pair in the acceptor stem of the mitochondrially encoded tRNAPhe in plants. In vitro processing of edited and unedited Oenothera tRNA Phe precursor RNAs with pea mitochondrial protein extracts shows a significant effect of this RNA-editing event on the efficiency of 5' and 3' processing. While mature tRNA molecules are rapidly generated by in vitro processing from edited precursors, the formation of mature tRNAs from unedited pre-tRNAs is considerably reduced. Primer extension analyses of in vitro processing products show that processing at both 5' and 3' termini is governed by the RNA-editing event. Investigation of edited and unedited precursor RNAs by lead cleavage experiments reveals differences in the higher order structures of the pre-tRNAs. The differing conformations are most likely responsible for the altered processing efficiencies of edited and unedited precursor molecules. RNA editing of the tRNAPhe precursors is thus a prerequisite for efficient excision of the mature tRNAPhe in vitro. Hence RNA editing might be involved in regulating the amount of mature tRNAPhe in the steady state RNA pool of mitochondria in higher plants.

Amino Acid Sequence↗

PubMed2005

Medical findings in outpatients with anorexia nervosa.

BACKGROUND: Approximately 0.5% to 1% of college-aged women have anorexia nervosa and most of them live in the community. However, few clinical data exist regarding community-dwelling women with anorexia nervosa. The objective of this study was to determine the prevalences of common medical findings for these women. METHODS: Cross-sectional, community-based study of 214 women with anorexia nervosa as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). Participants were recruited through advertisements and community-based referrals to a study investigating skeletal health in outpatients with anorexia nervosa. RESULTS: The prevalences of medical findings among the 214 participants were as follows: anemia, 38.6%; leukocytopenia, 34.4%; hyponatremia, 19.7%; hypokalemia, 19.7%; bradycardia, 41.3%; hypotension, 16.1%; hypothermia, 22.4%; elevation of alanine aminotransferase concentration, 12.2%; osteopenia, 51.7%; osteoporosis, 34.6%; and primary amenorrhea, 14.8%. Moreover, 30% of the women reported histories of bone fractures. Except for leukocytopenia (P = .01), bone loss (P = .04), and bradycardia (P = .01), the probability of specific medical findings could not be predicted by the degree of undernutrition. CONCLUSIONS: These results demonstrate a high prevalence of medical findings in community-dwelling women with anorexia nervosa. Therefore, women with anorexia nervosa should be carefully followed up with regular physical examinations and laboratory assessments. In addition, low weight, particularly in conjunction with the abnormalities reported, should prompt the consideration of a diagnosis of anorexia nervosa.

Absorptiometry, Photon↗

PubMed2014

Gene therapy for the nervous system: challenges and new strategies.

Current clinical treatments for central nervous system (CNS) diseases, such as Parkinson's disease and glioblastoma do not halt disease progression and have significant treatment morbidities. Gene therapy has the potential to "permanently" correct disease by bringing in a normal gene to correct a mutant gene deficiency, knocking down mRNA of mutant alleles, and inducing cell-death in cancer cells using transgenes encoding apoptosis-inducing proteins. Promising results in clinical trials of eye disease (Leber's congenital aumorosis) and Parkinson's disease have shown that gene-based neurotherapeutics have great potential. The recent development of genome editing technology, such as zinc finger nucleases, TALENS, and CRISPR, has made the ultimate goal of gene correction a step closer. This review summarizes the challenges faced by gene-based neurotherapeutics and the current and recent strategies designed to overcome these barriers. We have chosen the following challenges to focus on in this review: (1) delivery vehicles (both virus and nonviral), (2) use of promoters for vector-mediated gene expression in CNS, and (3) delivery across the blood-brain barrier. The final section (4) focuses on promising pre-clinical/clinical studies of neurotherapeutics.

Animals↗

PubMed1995

String editing analysis of human visual search.

Eye movement (EM) data were recorded for human subjects performing a visual search task in a stereoscopic computer-generated three-dimensional scene. Each experimental run consisted of six presentations: three different object placements on a common background (quasi-natural scene) were used and one of the placements was repeated three additional times. Raw EM searchpath data were linearized, fixation points were defined via a fixation algorithm and, finally, strings of fixation region labels were obtained based upon a priori regionalization schemes. Use of string editing techniques allowed quantitative comparison of the similarity of various searchpaths. Analysis of the similarity of searchpaths for each subject, as well as across subjects, led us to conclude that presentation of repeated object placements caused each subject to develop a partly self-consistent, but idiosyncratic searchpath based upon a spatial model for that placement pattern.

Algorithms↗

PubMed1995

SAM: a system for iteratively building marker maps.

SAM (system for assembling markers) is a system which supports man-machine problem solving for iteratively ordering a set of markers. SAM aids the user in partially ordering a set of markers based on incomplete and uncertain data. As data is added and modified, SAM aids the user in updating the previously assembled maps. The input is a file of clones and for each clone, a list of the markers contained within it. The objective is to order the set of markers such that the markers contained in each clone are consecutive. The user directs the map building by selecting functions to assemble a region of markers, order the clones to fit the order of the markers and position new markers within an ordered set of markers. The user can edit the input data, edit the assembled map and add clones to the map based on their marker content. The results are displayed graphically and can be saved in a solution file. Based on the partial map, the user designs new experiments or edits the existing data to fill gaps and resolve ambiguities. When a previously assembled map is loaded into SAM, it is automatically updated with the new or altered data. SAM treats all markers as points, but has special features for multiple copy and long markers so that they can be used in the map building process. This system has supported the building of a YAC map of human chromosome 22 at the Sanger Centre, where use of Alu-PCR product markers is a major component in determining clone overlap and where we have an on-going effort to accumulate data from various sources. SAM is also being used at various other laboratories.

Algorithms↗

PubMedDate not supplied

Training similarity measures for specific activities: application to reduced graphs.

Reduced graph representations of chemical structures have been shown to be effective in similarity searching applications where they offer comparable performance to other 2D descriptors in terms of recall experiments. They have also been shown to complement existing descriptors and to offer potential to scaffold hop from one chemical series to another. Various methods have been developed for quantifying the similarity between reduced graphs including fingerprint approaches, graph matching, and an edit distance method. The edit distance approach quantifies the degree of similarity of two reduced graphs based on the number and type of operations required to convert one graph to the other. An attractive feature of the edit distance method is the ability to assign different weights to different operations. For example, the mutation of an aromatic ring node to an acyclic node may be assigned a higher weight than the mutation of an aromatic ring to an aliphatic ring node. In this paper, we describe a genetic algorithm (GA) for training the weights of the different edit distance operations. The method is applied to specific activity classes extracted from the MDDR database to derive activity-class specific weights. The GA-derived weights give substantially improved results in recall experiments as compared to using weights assigned on intuition. Furthermore, such activity specific weights may provide useful structure--activity information for subsequent design efforts. In a virtual screening setting when few active compounds are known, it may be more useful to have weights that perform well across a variety of different activity classes. Thus, the GA is also trained on multiple activity classes simultaneously to derive a generalized set of weights. These more generally applicable weights also represent a substantial improvement on previous work.

Algorithms↗

PubMed2003

A platform to develop and to improve effectiveness of online computable guidelines.

The quality criteria of guidelines are identified. Taking these criteria into account we have built a platform to improve computable guideline effectiveness and facilitate their production. Our implementation is based on the GLIF Model (GuideLine Interchange Format). We have designed software components to edit, test, index, perform and present guidelines in a user-friendly Web architecture. These components are based on XML specifications in order to preserve their shareability and their re-usability. Several guidelines have been developed using our approach. We discuss the advantages of such an implementation and future evolutions so as to improve guideline integration within the clinician's workflow.

Decision Support Systems, Clinical↗