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 1,459 records · Page 81Linked to original sources

[Sexuality. A freudian psychoanalytical concept].

Emphasis is placed in the difficulty in conceptualizing sexuality as a complex and controversial subject. This is a presentation of a concept based on freudian psychoanalysis. With this in mind, many of Freud's references are collected from the Brazilian Standard Edition of the Complete Psychological Works of Sigmund Freud. The following concept is arrived at: sexuality is an instinctive vital energy directed to pleasure, with the possibility of quantitative and qualitative variations, closely bound to homeostasis, to affection, to social relations, to phases of development of childhood-libido, to eroticism, to genitality, to sexual relations, to procreation and to sublimation.

Cathexis↗

[Leprosy situation in Myanmar before and after multidrug therapy].

We introduced history of leprosy in Myanmar based on the book of Myanmar Academy of Medical Science published entitled "CONQUEST OF SCOURGES IN MYANMAR (Complied and Edited by Ko Ko, Kyaw and U Thaung) at 2002. "Leprosy Elimination Programme in Myanmar (Kyaw Lwin and Kyaw Nyunt Stein)" was appeared at chapter III in it. After dapsone treatment appeared, leprosy control program has started. Health system and service were developed and leprosy control program was also included in them. The integration of the elimination activities into basic health workers, such as midwives and health volunteers, has enabled the participation of a wide range of people in the community. After 1990s, multidrug therapy (MDT) was covered whole area of Myanmar, and task force for leprosy elimination was formed at Sate/Division, District and Township level. Finally Myanmar achieved the elimination of leprosy in January in 2003.

Dapsone↗

[Study on releasing rate of chrysophanol from Ruyi Jinhuang plaster].

OBJECTIVE: To study the releasing rate of chrysophanol from Ruyi Jinhuang plaster. METHOD: Based on the detecting methods of releasing rate and residual dosage applied in (Pharmacopoeia of P. R. C) (2000 edition), the contents of chrysophanol were detected by HPLC. RESULT: Chrysophanol in Ruyi Jinhuang plaster could well be released from plaster and to form medicinal concentration gradient. CONCLUSION: Chrysophanol in Ruyi-Jinhuang plaster can possibly be absorbed by skin.

Administration, Cutaneous↗

[Capacity of monitoring system on birth defects during 1990s in China].

OBJECTIVE: To understand the status and capacity of monitoring system on birth defects in China. METHODS: Data regarding 27 groups of birth defects from 57 monitoring programs in World Atlas of Birth Defects (2nd Edition) published by WHO/ICBDMS/EUROCAT/HGP and descriptive analysis by their ranking and contribution were carried out. RESULTS: Both hospital-based (Chinese Birth Defects Monitoring Network, CBDMN) and population-based (Birth Defect Surveillance System in Thirty Counties of Four Provinces, Beijing) monitoring systems showed the same characteristics as below: (1) Not enough groups were monitored, with trisomy 13/18 and congenital heart disease not reported. (2) Prevalence on those 'easily observed' group was high and cleft lip with or without cleft palate in CBDMN ranked 5 among 57 programs, with similar situation in polydactyly. (3) While prevalence rates of internal system and choromosal anomaly were low, CBDMN ranked 56 with Beijing the only non-reported city among all the 57 programs. (4) Unreasonable relationship was seen with prevalence of cleft lip was 5.76,4.02 times higher than that of cleft palate in CBDMN and in Beijing program. Which was 1.58 times of the world's means. Prevalence rates of anencephaly and total anotia/microtia rose 10.39% while spina bifida, hydrocephaly, and gastroschisis had a 4%-5% increase. The prevalence of hypospadias decreased by 4.13% and Down syndrome by 3.02%. CONCLUSION: The capacity of birth defects monitoring, both hospital-based and population-based, was poor in the 1990s, in China.

Capacity Building↗

Coverage of sixty core veterinary medical journals by ten indexing and abstracting tools.

Ten indexing and abstracting reference sources were examined for their coverage of 60 core veterinary medical journals. The costs of the indexes also were compared. Coverage of the 60 core veterinary journals ranged from 8 of 60 journals by Current Contents--Life Sciences to 57 of 60 by Index Veterinarius. Based on yearly costs, format, and coverage of the 60 core veterinary journals, Small Animal Practice and the 2 editions of Veterinary Reference Service were determined to be the most useful for private practitioners. The Index Veterinarius gives the most complete coverage of the core veterinary journals for veterinary research workers who have access to a library.

Abstracting and Indexing↗

Basic journal list for small hospital libraries.

This Basic Journal List of forty-eight journal titles is intended as a selection guide for the librarian of the small hospital. It is based on a survey of physicians in Virginia who were asked to review journal titles contained in the 1967 edition of a list compiled by Mr. Alfred N. Brandon. The List is designed for the library in a hospital of from 100 to 300 beds and for the active clinician.

Libraries, Hospital↗

Structure and sequence determinants required for the RNA editing of ADAR2 substrates.

ADAR2 is a double-stranded RNA-specific adenosine deaminase involved in the editing of mammalian RNAs by the site-specific conversion of adenosine to inosine. We have demonstrated previously that ADAR2 can modify its own pre-mRNA, leading to the creation of a proximal 3'-splice junction containing a non-canonical adenosine-inosine (A-I) dinucleotide. Alternative splicing to this proximal acceptor shifts the reading frame of the mature mRNA transcript, resulting in the loss of functional ADAR2 expression. Both evolutionary sequence conservation and mutational analysis support the existence of an extended RNA duplex within the ADAR2 pre-mRNA formed by base-pairing interactions between regions approximately 1.3-kilobases apart in intron 4 and exon 5. Characterization of ADAR2 pre-mRNA transcripts isolated from adult rat brain identified 16 editing sites within this duplex region, and sites preferentially modified by ADAR1 and ADAR2 have been defined using both tissue culture and in vitro editing systems. Statistical analysis of nucleotide sequences surrounding edited and non-edited adenosine residues have identified a nucleotide sequence bias correlating with ADAR2 site preference and editing efficiency. Among a mixed population of ADAR substrates, ADAR2 preferentially favors its own transcript, yet mutation of a poor substrate to conform to the defined nucleotide bias increases the ability of that substrate to be modified by ADAR2. These data suggest that both sequence and structural elements are required to define adenosine moieties targeted for specific ADAR2-mediated deamination.

Adenosine Deaminase↗

Hepatitis delta virus RNA editing is highly specific for the amber/W site and is suppressed by hepatitis delta antigen.

RNA editing at adenosine 1012 (amber/W site) in the antigenomic RNA of hepatitis delta virus (HDV) allows two essential forms of the viral protein, hepatitis delta antigen (HDAg), to be synthesized from a single open reading frame. Editing at the amber/W site is thought to be catalyzed by one of the cellular enzymes known as adenosine deaminases that act on RNA (ADARs). In vitro, the enzymes ADAR1 and ADAR2 deaminate adenosines within many different sequences of base-paired RNA. Since promiscuous deamination could compromise the viability of HDV, we wondered if additional deamination events occurred within the highly base paired HDV RNA. By sequencing cDNAs derived from HDV RNA from transfected Huh-7 cells, we determined that the RNA was not extensively modified at other adenosines. Approximately 0.16 to 0.32 adenosines were modified per antigenome during 6 to 13 days posttransfection. Interestingly, all observed non-amber/W adenosine modifications, which occurred mostly at positions that are highly conserved among naturally occurring HDV isolates, were found in RNAs that were also modified at the amber/W site. Such coordinate modification likely limits potential deleterious effects of promiscuous editing. Neither viral replication nor HDAg was required for the highly specific editing observed in cells. However, HDAg was found to suppress editing at the amber/W site when expressed at levels similar to those found during HDV replication. These data suggest HDAg may regulate amber/W site editing during virus replication.

Base Sequence↗

Processing of plant mitochondrial tRNAGly and tRNASer(GCU) is independent of RNA editing.

The genes encoding pea and potato mitochondrial tRNAGly and pea mitochondrial tRNASer(GCU) were analyzed with particular respect to their expression. Secondary-structure models deduced from the identical potato and pea tRNAGly gene sequences revealed A7:C66 mismatches in the seventh base pair at the base of the acceptor stems of both tRNAs. Sequence analyses of tRNAGly cDNA clones showed that these mispairings are not corrected by C66 to U66 conversions, as observed in plant mitochondrial tRNAPhe. Likewise, a U6:C67 mismatch identified in the acceptor stem of the pea tRNASer(GCU) is not altered by RNA editing to a mismatched U:U pair, which is created by RNA editing in Oenothera mitochondrial tRNACys. In vitro processing reactions with the respective tRNAGly and tRNASer(GCU) precursors show that such conversions are not necessary for 5' and 3' end maturation of these tRNAs. These results demonstrate that not all C:A (A:C) or U:C (C:U) mismatches in double-stranded regions of tRNAs are altered by RNA editing. An RNA editing event in plant mitochondrial tRNAs is thus not generally indicated by the presence of a mismatch but may depend on additional parameters.

Cloning, Molecular↗

[Dilemmas of the pharmacist, 7th edition of Hungarian National Formulary in practice].

Most important event of year 2004 of the history of Hungarian pharmacy was the release of the 7th edition of the National Formulary. The general part of the new formulary expanded, remarks on the preparations are more detailed and dispensing technologies are more elaborated. Knowledge base on pharmaceutical substances and incompatibility is inserted as novelty. Following the principles of modern pharmacy practice the new National Formulary excludes pills, though it is still accepted as an alternative dosage form. Usage of tablets, hard gelatine capsules and medication stick as a new dosage forms are introduced. The aim of my study was to prepare and examine some new compositions of the new edition of the National Formulary to help the pharmacist's work. Results confirmed the novel solutions of the new National Formulary.

Formularies as Topic↗

DNA sequence analysis of the complete mitochondrial genome of the green alga Scenedesmus obliquus: evidence for UAG being a leucine and UCA being a non-sense codon.

The complete DNA sequence of the mitochondrial genome of the chlorophyceen alga Scenedesmus obliquus was determined. The circular genome of 42781bp contains a basic set of 13 mitochondrial genes, which are conserved among plant or algal chondriomes. In addition, two scrambled rRNA and 27 tRNA genes are present, together with four intronic sequences (group I and II) and five open reading frames (ORFs), which show no significant homology to other ORFs from organellar genomes. The comparison with deduced amino acid sequences from 13 conserved mitochondrial genes gives rise to the conclusion that two deviations from the standard genetic code must be present in S. obliquus mitochondria: (i) UAG codes for leucine as was already found in some other algal mitochondria; (ii) UCA is a stop codon, which seems unique for mitochondrial genomes. This was supported by our finding that a tRNA-Leu gene possesses a UCA anticodon and by a missing tRNA-serine, able to decode the UCA codon. Consistent with these data is the absence of any UCA codon from conserved mitochondrial ORFs. This codon occurs only close to the end of all ORFs, while UAA or UGA codons are found at some distance from any conserved ORF. Codon changes by RNA editing can be excluded, since RT-PCR analysis does not reveal any evidence for post-transcriptional RNA modifications of the primary transcript.

Algal Proteins↗

The RNA-editing enzyme ADAR1 is localized to the nascent ribonucleoprotein matrix on Xenopus lampbrush chromosomes but specifically associates with an atypical loop.

Double-stranded RNA adenosine deaminase (ADAR1, dsRAD, DRADA) converts adenosines to inosines in double-stranded RNAs. Few candidate substrates for ADAR1 editing are known at this point and it is not known how substrate recognition is achieved. In some cases editing sites are defined by basepaired regions formed between intronic and exonic sequences, suggesting that the enzyme might function cotranscriptionally. We have isolated two variants of Xenopus laevis ADAR1 for which no editing substrates are currently known. We demonstrate that both variants of the enzyme are associated with transcriptionally active chromosome loops suggesting that the enzyme acts cotranscriptionally. The widespread distribution of the protein along the entire chromosome indicates that ADAR1 associates with the RNP matrix in a substrate-independent manner. Inhibition of splicing, another cotranscriptional process, does not affect the chromosomal localization of ADAR1. Furthermore, we can show that the enzyme is dramatically enriched on a special RNA-containing loop that seems transcriptionally silent. Detailed analysis of this loop suggests that it might represent a site of ADAR1 storage or a site where active RNA editing is taking place. Finally, mutational analysis of ADAR1 demonstrates that a putative Z-DNA binding domain present in ADAR1 is not required for chromosomal targeting of the protein.

Adenosine Deaminase↗

City tests and information theory.

The responses of 455 male subjects on both editions of the City University Colour Vision Tests (City 1 and City 2) were recorded after the establishment of each subject's criterial status using the Nagel anomaloscope. Based on the Information Theory, each plate was assigned a contributory weighted score to the total test score. Using informational analysis, a cut-off point in test score separating normals and defectives was also determined for each test. This scoring system is an improvement on the existing (or manufacturer's) system. The analysis has also shown that the second edition (City 2) is a considerable improvement on the first (City 1). Despite this, even the improved City 2, like its origin, the D-15, is shown to be poorer than most of the commonly used PIC tests.

Adolescent↗

Molecular profiling of pancreatic acinar cell carcinoma and amphicrine-like carcinoma: high frequency of homologous recombination deficiency and molecular heterogeneity.

BACKGROUND: The 6th edition of the WHO Classification of Digestive System Tumours distinguishes amphicrine-like carcinomas (ALCs) from mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs). Acinar cell carcinomas (ACCs) with an intimately admixed and not separated neuroendocrine component comprising >30% of the tumour are classified as amphicrine-like ACCs (AL-ACCs). We characterised the genomic landscape of pancreatic ACCs and AL-ACCs to validate current classification and identify therapeutic targets. METHODS: Among 2,151 pancreatic biopsy and resection cases that underwent targeted next-generation sequencing using the OncoPanel AMC v4.3 or v4.5 (DNA-based hybrid capture, targeting 323 genes (v4.3) or 343 genes (v4.5)), eight ACCs, seven AL-ACCs originally diagnosed as MiNENs under the 5th edition of the WHO classification scheme, and four neuroendocrine tumours (NETs) were identified, diagnosed between 2020 and 2026. RESULTS: Homologous recombination deficiency (HRD)-associated alterations, involving BRCA1/2, ATM and FANCD2, were identified in 87.5% (7/8) of ACCs and 29% of AL-ACCs. One ACC had an ATRX nonsense mutation. Genomic heterogeneity was observed in molecular profiling of AL-ACCs; two demonstrated a 'true hybrid' signature with co-occurrence of lineage-specific drivers: MEN1 deletion and splice site mutation (neuroendocrine-associated), APC, SMAD4 and CTNNB1 alterations (exocrine-associated). Two others exhibited 'ACC-like' signatures, including missense BRCA1 and nonsense TP53 mutations and MDM4 and AKT3 amplifications, located on chromosome 1q, despite their neuroendocrine differentiation. CONCLUSIONS: Pancreatic ACCs frequently harbour HRD-related alterations, suggesting potential for PARP-inhibitor therapy. AL-ACCs comprise molecularly heterogeneous groups, including true hybrid and ACC-like patterns. Larger studies are required to elucidate the molecular distinction between true hybrid AL-ACCs and those with single-lineage alterations to refine their classification.

acinar↗

Creation of an initiation codon by RNA editing in the coxI transcript from tomato mitochondria.

Nucleotide-sequence analysis showed that the gene for cytochrome oxidase subunit I (coxI) from tomato mitochondrial DNA has an ACG codon at a conserved position corresponding to an ATG initiation codon in other higher-plant coxI genes. cDNA-sequence analysis of the coxI transcripts showed that 15 positions in the genomic DNA were converted from C to U in the transcripts by RNA editing. One of the editing events is observed at the indicated ACG codon, producing an ATG initiation codon. The nucleotide sequences of 37 cDNA clones showed that the initiation codon was created in 32 out of the 37 clones, while nucleotide positions 254 and 11 were edited in 37 and 34 of the 37 clones examined, respectively, suggesting that creation of the initiation codon is a post-transcriptional event. The BamHI site at nucleotide position 757-762 within the coxI genomic DNA was altered in all 97 cDNA clones examined, demonstrating that RNA editing at this site in the transcripts is very common. RNA editing takes place to a lesser extent at the initiation codon, compared with editing at internal position 254. This indicates that editing is either a random process or that it involves a mechanism favoring less RNA editing in the initiation codon than in internal sites.

Amino Acid Sequence↗

Purification and assay of recombinant ADAR proteins expressed in the yeast Pichia pastoris or in Escherichia coli.

ADARs are found in Metazoans but are not present in yeasts. We have found that the methanol-utilizing yeast Pichia pastoris can be used to efficiently express enzymatically active epitope-tagged ADARs. We describe plasmid construction and protein expression procedures for producing Drosophila ADAR in this system.ADAR expression in Pichia pastoris uses the methanol-inducible alcohol oxidase AOX1 promoter for induction. A Zeocin resistance gene on the plasmid is used to select high copy number tandem integrations of the plasmid constructs. Preparation of extracts by grinding cultures in liquid nitrogen and purification protocols using 6 x HIS and FLAG epitope tags are described. Procedures for preparing radiolabeled dsRNA and for assaying the non-specific RNA editing activity of ADARs are described.ADARs produced in Escherichia coli are not enzymatically active. We describe expression of the ADAR dsRNA binding domains in E. coli using current versions of the T7 promoter based Studier vectors as well as the purification of the domains.

Adenosine Deaminase↗

A present-day aminoacyl-tRNA synthetase with ancestral editing properties.

Leucyl-, isoleucyl-, and valyl-tRNA synthetases form a subgroup of related aminoacyl-tRNA synthetases that attach similar amino acids to their cognate tRNAs. To prevent amino acid misincorporation during translation, these enzymes also hydrolyze mischarged tRNAs through a post-transfer editing mechanism. Here we show that LeuRS from the deep-branching bacterium Aquifex aeolicus edits the complete set of aminoacylated tRNAs generated by the three enzymes: Ile-tRNA(Ile), Val-tRNA(Ile), Val-tRNA(Val), Thr-tRNA(Val), and Ile-tRNA(Leu). This unusual enlarged editing property was studied in a model of a primitive editing system containing a composite minihelix carrying the triple leucine, isoleucine, and valine identity mimicking the primitive tRNA precursor. We found that the freestanding LeuRS editing domain can edit this precursor in contrast to IleRS and ValRS editing domains. These results suggest that A. aeolicus LeuRS carries editing properties that seem more primitive than those of IleRS and ValRS. They suggest that the A. aeolicus editing domain has preserved the ambiguous editing property from the ancestral common editing domain or, alternatively, that this plasticity results from a specific metabolic adaptation.

Bacteria↗