Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Base editing”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 523 records · Page 29Linked to original sources
PubMed2026

Disruption of CTCF binding by germline non-coding variants in CDKN2B suppress CDKN2A expression and predispose to melanoma.

Some melanoma-prone families linked to the 9p21 locus, harboring the established susceptibility gene CDKN2A, lack pathogenic protein-coding variants. Using whole-exome and targeted sequencing, we identified three rare single-nucleotide variants in two melanoma-prone families and one sporadic melanoma case. Variants map to a conserved CTCF-bound region within the first intron of CDKN2B that physically interacts with CDKN2A. Analysis of UK Biobank showed significant enrichment of variants in this region in melanoma cases. Variants result in diminished CTCF binding in vitro. CTCF ChIP-seq in fibroblasts from the carriers of the largest family demonstrated loss of CTCF binding, accompanied by weakened promoter interactions and allele-specific reduction of CDKN2A p16 transcript expression from the variant haplotype. CRISPR-based perturbation of this region and editing of the large family variant into melanocytes resulted in reduced expression of p14 and p16 CDKN2A transcripts. These findings suggest that non-coding regulatory variants function as high-penetrance susceptibility alleles in melanoma families by altering CDKN2A function.

Journal Article↗
PubMed2000

Auras, seizure focus, and psychiatric disorders.

OBJECTIVE: The goal of this study was to assess the types of auras and their associations with the focus of seizures in 144 consecutive adult patients with partial epilepsy refractory to medical treatment. The association of frequency and type of aura with a psychiatric disorder was also studied. BACKGROUND: The nature of the aura, its association with the seizure focus, and its relation with emotions and behavioral dysfunction have received relatively little attention, and remain controversial. METHODS: Patients were admitted to an epilepsy investigation unit for detailed observation of their seizures and type of aura. Patients underwent standard electroencephalographic telemetry, including implanted subdural electrodes, if necessary, to delineate the seizure focus. The auras were classified into nine categories. All patients had an independent clinical psychiatric interview for a Diagnostic and Statistical Manual, Third Edition-Revised (DSM-III-R)-based diagnosis. RESULTS: Of the 144 patients studied, 111 (77.1%) had one or more symptoms during the aura and 33 (22.9%) had no aura. The most frequent aura types were viscerosensory (47 cases [32.6%]), experiential (44 cases [30.6%]), and cephalic (21 cases [14.6%]). A temporal lobe focus was present in 116 (80.5%) patients. Only experiential auras were significantly associated with a temporal lobe seizure focus (33 of 44 cases). A DSM-III-R psychiatric diagnosis was present in 74 (51.4%) patients. Of the 116 patients with a temporal lobe focus, 60 (50.2%) had a DSM-III-R psychiatric diagnosis. Patients with two or more auras were significantly more likely to have a psychiatric diagnosis (70.2%) compared with those with one aura (39.1%) or no aura (48.5%). A significant association between experiential auras and psychiatric morbidity was seen. CONCLUSIONS: Auras occurred in a majority of patients with a treatment-refractory partial epilepsy who were hospitalized for assessment of their seizure focus for possible surgical candidacy. Two or more auras were associated with a psychiatric diagnosis as was the presence of an experiential aura. Experiential auras were most common in temporal lobe epilepsy. Approximately half the patients, irrespective of seizure focus, had an associated psychiatric morbidity.

Adolescent↗
PubMed1992

[The original of the "Tratado de Urología" by Francisco Díaz. Lost during the fire of the Monastery of El Escorial in 1671?].

The publication of the Treaty of Urology of Francisco Díaz towards the end of the sixteenth Century, was a milestone in the History of medicine. The originality and precociousness of his doctrine entailed a true revolution in the genesis of medicosurgical literature, considering that the text constitutes an inspired anticipation to the specialization age. Ever since the last century, all historians and annotators of this work have asked themselves whether there was an earlier edition to that of 1588 since the title "Newly printed treaty ..." invites such a inference. So far, every investigation searching for the original or a copy of the first edition have been in vain. This paper, based on documents and old works from the Archive of Protocols in Madrid, Library of the Royal Palace and Library of El Escorial Monastery, reveals certain data until now unpublished on the destiny of most of the copies belonging to the second edition presented and brings into light old references on which account is given that the original "Treaty of Urology" by Francisco Díaz, considered to be a Sixteenth Century Codex was lost in the fire of the El Escorial Monastery in 1671.

Fires↗
PubMed1994

Intimacy and science: the publication of clinical facts in psychoanalysis.

This paper starts by stating that in science there are no facts independent of theory. In psychoanalysis, the theory of the decisive importance of the unconscious makes it possible to grasp clinical facts. This leads to the centrality of transference in analysis. The latter is understood as a social fact. Transference, perceived as a private experience, can be known in the intimacy of the psychoanalytic relationship, through the communication by means of language, which is public. Psychoanalysis is then considered a science of intimacy. The analyst, in publishing clinical facts, faces the problem of the transposition of a fact from the intimacy sphere, considered as private, to the public sphere, and thus serves a scientific purpose. A treatment report is presented to illustrate the problems of the registering, editing and publishing of clinical facts, based on the parallel between making conscious that which is unconscious and making potentially public what is private. Thus the analyst confronts similar difficulties and anxieties, when publishing clinical facts, as the ones that the analysand must overcome to know, through the social experience of psychic intimacy, his or her private inner world.

Adult↗
PubMed1997

Nurse writers internet and World Wide Web sites.

Nurse writers can use the Internet to find vast amounts of current information on topics for professional articles. The following excerpts are based on concepts in the Second Edition of the authors' book, How to Write and Publish Articles in Nursing, published by Springer Publishing Company. The Second Edition will is now available.

Computer Communication Networks↗
PubMed1992

In vivo model for pseudo-templated transcription in Sendai virus.

A synthetic Sendai virus-like recombinant RNA was used to develop a model system for pseudo-templated transcription of the P/C gene. The synthetic RNA molecule contains a 42-base stretch of nucleotide sequence derived from the RNA editing site of the P/C gene embedded into the chloramphenicol acetyltransferase gene. When this construct was rescued into Sendai virus, it was found that this 42-base sequence was sufficient to allow the Sendai virus polymerase to transcribe mRNAs with G-nucleotide insertions. Edited mRNA species containing a single nontemplated G insertion were found at a frequency of 6.5%, while rare messages had two G residues inserted. Edited viral RNA was not apparent, suggesting that this event is appropriately excluded during replication of the model genome. By progressively deleting from the 3' end, we found that a 24-nucleotide sequence spanning the G-insertion site was sufficient for pseudo-templated transcription in our system.

Animals↗
PubMed1995

Editing of human alpha-galactosidase RNA resulting in a pyrimidine to purine conversion.

During a study of the gene coding for alpha-galactosidase (EC 3.2.1.22), the lysosomal enzyme deficient in Fabry's disease, RT-PCR amplification of alpha-galactosidase mRNAs obtained from three different tissues isolated from males revealed a substantial number of clones with a U to A conversion at the nucleotide position 1187. Such a modification of the coding sequence would result in an amino acid substitution in the C-terminal region (Phe396Tyr) of the enzyme. Neither PCR analysis of the genomic sequence nor the RT-PCR amplification of RNA obtained by in vitro transcription of the wild-type cDNA showed this change in the sequence. Multiple genes, pseudogenes are allelic variants were excluded. Hence, we propose RNA editing as a mechanism responsible for this base change in the alpha-galactosidase RNA.

Base Sequence↗
PubMed1996

Structural requirements for RNA editing in glutamate receptor pre-mRNAs by recombinant double-stranded RNA adenosine deaminase.

Pre-mRNAs for brain-expressed ionotropic glutamate receptor subunits undergo RNA editing by site-specific adenosine deamination, which alters codons for molecular determinants of channel function. This nuclear process requires double-stranded RNA structures formed by exonic and intronic sequences in the pre-mRNA and is likely to be catalyzed by an adenosine deaminase that recognizes these structures as a substrate. DRADA, a double-stranded RNA adenosine deaminase, is a candidate enzyme for L-glutamate-activated receptor channel (GluR) pre-mRNA editing. We show here that DRADA indeed edits GluR pre-mRNAs, but that it displays selectivity for certain editing sites. Recombinantly expressed DRADA, both in its full-length form and in an N-terminally truncated version, edited the Q/R site in GluR6 pre-mRNA and the R/G site but not the Q/R site of GluR-B pre-mRNA. This substrate selectivity correlated with the base pairing status and sequence environment of the editing-targeted adenosines. The Q/R site of GluR-B pre-mRNA was edited by an activity partially purified from HeLa cells and thus differently structured editing sites in GluR pre-mRNAs appear to be substrates for different enzymatic activities.

Adenosine↗
PubMed2005

Aminoacylation complex structures of leucyl-tRNA synthetase and tRNALeu reveal two modes of discriminator-base recognition.

Leucyl-tRNA synthetase (LeuRS) specifically recognizes the characteristic long variable arm and the discriminator base, A73, of tRNA(Leu) in archaea and eukarya. The LeuRS 'editing domain' hydrolyzes misformed noncognate aminoacyl-tRNA. Here we report the crystal structure of the archaeal Pyrococcus horikoshii LeuRS-tRNA(Leu) complex. The protruding C-terminal domain of LeuRS specifically recognizes the bases at the tip of the long variable arm. The editing domain swings from its tRNA-free position to avoid clashing with the tRNA. Consequently the tRNA CCA end can bend and reach the aminoacylation active site. The tRNA 3' region assumes two distinct conformations that allow A73 to be specifically recognized in different ways. One conformation is the canonical 'aminoacylation state.' The other conformation seems to be the 'intermediate state,' where the misaminoacylated 3' end has partially relocated to the editing domain.

Amino Acid Sequence↗
PubMed2001

Risk of dementia in Parkinson's disease: a community-based, prospective study.

OBJECTIVE: To calculate the incidence of and determine possible risk factors for dementia in PD. BACKGROUND: Dementia has important clinical consequences for patients with PD and their caregivers, but the incidence is unknown. METHODS: A population-based cohort of nondemented patients with PD (n = 171) from the county of Rogaland, Norway, was assessed at baseline and 4.2 years later with a comprehensive evaluation of motor, cognitive, and neuropsychiatric symptoms. The diagnosis of dementia was made according to the Diagnostic and Statistical Manual of Mental Disorders, 3rd edition, revised (DSM-III-R) criteria, based on interview of the patient and a caregiver, cognitive rating scales, and neuropsychologic tests. A representative sample of 3,062 nondemented elderly subjects without PD served as control group. RESULTS: Forty-three patients with PD were demented at follow-up evaluation, equivalent to an incidence rate of 95.3 per 1,000 person-years (95% CI, 68.2 to 122.0). The risk for the development of dementia in patients with PD relative to the control subjects after adjusting for age, sex, and education was 5.9 (95% CI, 3.9 to 9.1). Predictive factors at baseline for dementia in PD in addition to age were Hoehn & Yahr score >2 (OR, 3.4; 95% CI, 1.3 to 8.6) and Mini-Mental State Examination score < 29 (OR, 3.3; 95% CI, 1.3 to 8.2). CONCLUSIONS: Patients with PD have an almost sixfold increased risk for becoming demented compared with subjects without PD.

Aged↗
PubMed2026

High-efficiency genome-editing, transgene evaluation, and antimicrobial efficacy testing using Citrus medica L. hairy roots.

Huanglongbing (HLB) disease, associated with the fastidious bacterium Candidatus Liberibacter asiaticus (CLas), has a significant impact on citrus production worldwide. Conventional biochemical and genetic evaluation studies to identify potential disease resistance strategies have been mainly hindered due to the inability to culture CLas in a defined medium and the general recalcitrance of Citrus cultivars (grapefruits and oranges) to Agrobacterium-mediated plant transformation. We previously demonstrated the utility of plant hairy roots to co-cultivate CLas. In this study, we developed a hairy root transformation system using citron (Citrus medica L.), which is highly amenable to Rhizobium-mediated hairy root transformation. The explant survival and hairy root transformation efficiencies were up to 100% and 73%, respectively, and transgenic roots can be attained in as little as 30-60&#x2009;days. We demonstrate the utility of this citron-based hairy root transformation for rapid CRISPR/Cas9-mediated gene editing, transgene evaluation, and antimicrobial efficacy testing. The citron-based hairy root transformation system will significantly help the research community to speed-track the assessment of potential HLB disease resistance strategies.

Citrus↗
PubMed1994

Construction of a 28-mm 1H/13C probe and actively shielded Z-gradient set for operation in a 9.4 T/89 mm magnet.

In this work, we present a new RF and gradient assembly for operation in a 9.4 Tesla/89 mm magnet. This assembly was designed in order to enable 1H-NMR perfusion studies that are based on proton-observed carbon-edited approaches or gradient selected double quantum coherence. The RF portion of this probe assembly is comprised of a modified Alderman-Grant coil and a saddle coil operating at 400 and 100 MHz, respectively. These coils are surrounded by an actively shielded Z gradient, which also allows for the use of gradient-based water suppression without the need for carbon selection. We demonstrate that this probe can be used to implement gradient selected double quantum coherence experiments resulting in a high degree of water suppression.

Carbon Isotopes↗
PubMed2003

Death and the retrovirus.

A flurry of new papers has shown that HIV reverse transcription is vulnerable to G-->A hypermutation. Apparently, cytidine bases in nascent DNA synthesis are lethally edited by the host cell molecule apolipoprotein B editing complex protein (APOBEC) 3G. This death mechanism is circumvented by the HIV viral infectivity factor protein, which prevents APOBEC3G from entering the virion.

APOBEC-3G Deaminase↗
PubMed1997

Detection of mild dementia in community surveys. Is it possible to increase the accuracy of our diagnostic instruments?

OBJECTIVE: To investigate the accuracy of cognitive tests and clinical dementia diagnosis in distinguishing between mildly demented and nondemented subjects. DESIGN: Three-year longitudinal follow-up of a community-based cohort sample. Using the Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised as criterion variable, subjects were classified as demented and nondemented based on the results of cognitive test performance at time 1. These subjects were then examined prospectively for development of dementia at time 2. PARTICIPANTS: The sample consisted of 63 mildly demented (Mini-Mental State Examination score > 18 < 24) and 398 nondemented subjects at time 1. At follow-up, due to death and refusal of participation, the sample consisted of 108 demented and 217 nondemented subjects. RESULTS: The group of subjects who were considered to be demented according to the results of the cognitive tests and nondemented by the clinical diagnosis at time 1 had a higher incidence of dementia at time 2 than did the subjects who were considered to be nondemented according to both cognitive tests and clinical diagnosis. Among the incident dementia cases, subjects considered to be demented according to the cognitive tests but nondemented by the clinical diagnosis performed at a lower level on most cognitive tests were older, had less education, and consisted of more women than did the group of subjects who were considered to be demented by the clinical diagnosis and nondemented by the cognitive tests at time 1. CONCLUSIONS: A combination of cognitive tests, especially tasks assessing episodic memory, can detect many subjects in a preclinical state of dementia who could be missed in the clinical diagnostic procedure due to subjects' relatively high age, low education, and female sex. However, cognitive tests also may miss a sizable proportion of prevalent dementia cases due to possible insensitivity to the same demographic variables. These findings indicate the need of integration between clinical and cognitive data to increase the accuracy in detecting dementia in an early phase.

Aged↗
PubMed2005

C to U editing stimulates A to I editing in the anticodon loop of a cytoplasmic threonyl tRNA in Trypanosoma brucei.

Editing of tRNAs is widespread in nature and either changes the decoding properties or restores the folding of a tRNA. Unlike the phylogenetically disperse adenosine (A) to inosine (I) editing, cytosine (C) to uridine (U) editing has only been previously described in organellar tRNAs. We have shown that cytoplasmic tRNA(Thr)(AGU) undergoes two distinct editing events in the anticodon loop: C to U and A to I. In vivo, every inosine-containing tRNA(Thr) is also C to U edited at position 32. In vitro, C to U editing stimulates conversion of A to I at the wobble base. Although the in vivo and in vitro requirements differ, in both cases, the C to U change plays a key role in A to I editing. Due to an unusual abundance of A34-containing tRNAs, our results also suggest that the unedited and edited tRNAs are functional, each dedicated to decoding a specific threonine codon. C to U editing of cytoplasmic tRNA expands the editing repertoire in eukaryotic cells, and when coupled to A to I changes, leads to an interrelation between editing sites.

Animals↗
PubMed2000

Phantom-based performance evaluation: application to brain segmentation from magnetic resonance images.

This paper presents a new technique for assessing the accuracy of segmentation algorithms, applied to the performance evaluation of brain editing and brain tissue segmentation algorithms for magnetic resonance images. We propose performance evaluation criteria derived from the use of the realistic digital brain phantom Brainweb. This 'ground truth' allows us to build distance-based discrepancy features between the edited brain or the segmented brain tissues (such as cerebro-spinal fluid, grey matter and white matter) and the phantom model, taken as a reference. Furthermore, segmentation errors can be spatially determined, and ranged in terms of their distance to the reference. The brain editing method used is the combination of two segmentation techniques. The first is based on binary mathematical morphology and a region growing approach. It represents the initialization step, the results of which are then refined with the second method, using an active contour model. The brain tissue segmentation used is based on a Markov random field model. Segmentation results are shown on the phantom for each method, and on real magnetic resonance images for the editing step; performance is evaluated by the new distance-based technique and corroborates the effective refinement of the segmentation using active contours. The criteria described here can supersede biased visual inspection in order to compare, evaluate and validate any segmentation algorithm. Moreover, provided a 'ground truth' is given, we are able to determine quantitatively to what extent a segmentation algorithm is sensitive to internal parameters, noise, artefacts or distortions.

Algorithms↗
PubMed2006

Interactions of mRNAs and gRNAs involved in trypanosome mitochondrial RNA editing: structure probing of a gRNA bound to its cognate mRNA.

Expression of mitochondrial genes in Trypanosoma brucei requires RNA editing of its mRNA transcripts. During editing, uridylates are precisely inserted and deleted as directed by the gRNA template to create the protein open reading frame. This process involves the bimolecular interaction of the gRNA with its cognate pre-edited mRNA and the assembly of a protein complex with the enzymatic machinery required. While a considerable amount of work has been done identifying the protein components of the editing complex, very little is known about how a functional editosome is assembled. In addition, the importance of RNA structure in establishing a functional editing complex is poorly understood. Work in our lab suggests that different mRNA/gRNA pairs can form similar secondary structures suggesting that a common core architecture may be important for editosome recognition and function. Using solution structure probing, we have investigated the structure of the initiating gRNA, gCYb-558, in the mRNA/gRNA complex with pre-edited apocytochrome b mRNA. Our data indicate that the stem-loop formed by the guiding region of the gRNA alone is maintained in its interaction with the pre-edited message. In addition, our data suggest that a gRNA stem-loop structure is maintained through the first few editing events by the use of alternative base-pairing with the U-tail.

Animals↗