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Based on the arrangement of Renho Temple edition of Taisu (Extremely Plain), as an example, it can be seen that by correcting the wrong popular words in ancient medical books, the causes of mistakes of ancient editions and solution for annotations of difficult terms of ancient words in the medical books are of significance.
INTRODUCTION: The majority of Hungarian scientific results are published in international periodicals in foreign languages. Yet the publications in Hungarian scientific periodicals also should not be ignored. AIM: This study analyses biomedical periodicals of Hungarian edition from different points of view. METHODS: Based on different databases a list of titles consisting of 119 items resulted, which contains both the core and the peripheral journals of the biomedical field. These periodicals were analysed empirically, one by one: checking out the titles. RESULTS: 13 of the titles are ceased, among the rest 106 Hungarian scientific journals 10 are published in English language. From the remaining majority of Hungarian language and publishing only a few show up in international databases. Although quarter of the Hungarian biomedical journals meet the requirements, which means they could be represented in international databases, these periodicals are not indexed. 42 biomedical periodicals are available online. Although quarter of these journals come with restricted access. 2/3 of the Hungarian biomedical journals have detailed instructions to authors. These instructions inform the publishing doctors and researchers of the requirements of a biomedical periodical. CONCLUSIONS: The increasing number of Hungarian biomedical journals published is welcome news. But it would be important for quality publications which are cited a lot to appear in the Hungarian journals. The more publications are cited, the more journals and authors gain in prestige on home and international level.
The histologic or cytologic diagnosis of a tumoral lesion may be sometimes very difficult to do even for a senior pathologist. Nevertheless, it is necessary to recognize a malignant process with reliability and security. The usual way to solve some difficult problems is firstly to search documentations in books or atlas and then to discuss the slides in common. Sometimes it is necessary to dispatch the original documents to a national or international expert. Now computers are used in any private or public department of Pathology. Some new informatics developments allow to send good digitized pictures to an expert and to discuss with him. It is also possible to elaborate a data base of digitized images which can be edited on CD-Rom. We describe the development and the use of these technics in France and elsewhere. It seems that they could have an increasing role for quality assurance in tumoral pathology.
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MOTIVATION: Some organisms edit their messenger RNA resulting in differences between the genomic sequence for a gene and the corresponding messenger RNA sequence. This difference complicates experimental and computational attempts to find and study genes in organisms with RNA editing even if the full genomic sequence is known. Nevertheless, knowledge of these editing sites is crucial for understanding the editing machinery of these organisms. RESULTS: We present a computational technique that predicts the position of editing sites in the genomic sequence. It uses a statistical approach drawing on the protein sequences of related genes and general features of editing sites of the organism. We apply the method to the mitochondrion of the slime mold Physarum polycephalum. It correctly predicts over 90% of the amino acids and over 70% of the editing sites.
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RNA editing is a process whereby nucleotide insertion, deletion, or base substitution results in the production of an RNA whose sequence differs from that of its template. The mitochondrial RNAs of Physarum polycephalum are processed specifically at multiple sites by both mono- and dinucleotide insertions, as well as apparent cytidine (C) to uridine (U) changes. The precise mechanism and timing of these processing events are currently unknown. We describe here the development of an isolated mitochondrial system in which exogenously supplied nucleotides can be incorporated into RNAs under defined conditions. The results of S1 nuclease protection, nearest neighbor and RNase T1 fingerprint analyses indicate that the vast majority of these newly synthesized mitochondrial RNAs have been accurately and efficiently processed by both mono- and dinucleotide insertions. This work provides a direct demonstration of faithful nucleotide insertion in a mitochondrial editing system. In contrast, the newly synthesized RNAs are not processed by C to U changes in the isolated mitochondria, suggesting that the base changes observed in Physarum are unlikely to occur via a deletion/insertion mechanism.
The coding sequence of several mitochondrial mRNAs of the kinetoplastid protozoa is created through the insertion and deletion of specific uridylates. The editing reactions are required to be highly specific in order to ensure that functional open reading frames are created in edited mRNAs and that potentially deleterious modification of normally nonedited sequence does not occur. Selection-amplification and mutagenesis were previously used to identify the optimal sequence requirements for in vitro editing. There is, however, a minority of natural editing sites with suboptimal sequence. Several cis-acting elements, obtained from an in vitro selection, are described here that are able to compensate for a suboptimal editing site. An A + U sequence element within the 5'-untranslated region of cytochrome b mRNA from Leishmania tarentolae is also demonstrated to function as a cis-acting guide RNA and is postulated to compensate for a suboptimal editing site in vivo. Two proteins within an enriched editing extract are UV-cross-linked to two different in vitro selected editing substrates more efficiently than poorly edited RNAs. The results suggest that these proteins contribute to the specificity of the editing reaction.
RNA editing by extensive uridine addition and deletion creates over 90% of the amino acid codons in the cytochrome-c oxidase subunit III (COIII) transcript in Trypanosoma brucei and Herpetomonas, whereas editing of the COIII transcripts in Leishmania tarentolae and Crithidia fasciculata generates only 6% of the amino acid codons and is limited to the 5' ends. Is extensive RNA editing a primitive or derived character? We constructed a phylogenetic tree based on nuclear small-subunit and mitochondrial large- and small-subunit ribosomal RNA sequences for nine species of kinetoplastid protozoa. Our results suggest that extensive editing is a primitive genetic phenomenon that has disappeared in recent evolutionary time and also that there have been multiple losses of the digenetic lifestyle by loss of the vertebrate host in parasite evolution.
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Synthetic pre-edited messenger RNA (mRNA) and guide RNA (gRNA) for the 5'-edited maxicircle-encoded ND7 cryptogene from Leishmania tarentolae formed chimeric molecules upon incubation in the presence of a mitochondrial extract. These chimeric molecules consisted of the gRNAs covalently linked to the mRNAs by short oligo(U) tails at normal editing sites in most cases. Unlike the previously reported chimeras present in steady-state kinetoplast RNA, the in vitro-synthesized chimeras showed no editing of downstream editing sites. The synthesis of chimeric RNAs required ATP and was dependent on the formation of a gRNA/mRNA anchor duplex 3' of the pre-edited region, as shown by in vitro mutagenesis of the mRNA and the gRNA. mRNA sequences 3' and 5' of the pre-edited region also affected the efficiency of the chimera-forming activity. This in vitro system may accurately represent the initial step in RNA editing.
In common with other DNA polymerases, DNA polymerase III holoenzyme of E. coli selects the biologically correct base pair with remarkable accuracy. DNA polymerase III is particularly useful for mechanistic studies because the polymerase and editing activities reside on separate subunits. To investigate the biochemical mechanism for base insertion fidelity, we have used a gel electrophoresis assay to measure kinetic parameters for the incorporation of correct and incorrect nucleotides by the polymerase (alpha) subunit of DNA polymerase III. As judged by this assay, base selection contributes a factor of roughly 10(4)-10(5) to the overall fidelity of genome duplication. The accuracy of base selection is determined mainly by the differential KM of the enzyme for correct vs. incorrect deoxynucleoside triphosphate. The misinsertion of G opposite template A is relatively efficient, comparable to that found for G opposite T. Based on a variety of other work, the G:A pair may require a special correction mechanism, possibly because of a syn-anti pairing approximating Watson-Crick geometry. We suggest that precise recognition of the equivalent geometry of the Watson-Crick base pairs may be the most critical feature for base selection.
BACKGROUND: Inherited variants in the LDL (low-density lipoprotein) receptor (LDLR) gene are the most common cause of familial hypercholesterolemia, significantly increasing coronary artery disease risk. Early identification of pathogenic LDLR variants enables prompt lipid-lowering therapy and cascade testing of at-risk relatives; however, most LDLR variants observed in the population have uncertain or absent clinical classifications, leaving many patients without actionable information. METHODS: We developed the first activity-normalized prime editing screening pipeline to measure the impact of 5184 LDLR coding variants on LDL-cholesterol (LDL-C) uptake. Each prime editing guide RNA is paired with a genotypic outcome reporter to correct for variable editing efficiency, overcoming a key limitation of previous pooled genome editing screens. A statistical framework further improves variant effect estimates by jointly analyzing all missense variants at each amino acid position. RESULTS: We show that prime editing of the reporter construct correlates with endogenous variant installation frequency, validating the activity normalization approach. The resulting scores capture a continuous spectrum of functional effects, robustly separate pathogenic versus benign ClinVar variants, and show concordance with LDL-C levels in UK Biobank participants. We calibrate functional evidence strengths to the ACMG/AMP variant interpretation framework, enabling integration into a clinical variant classification workflow. By combining functional, computational, population, and contextual evidence, 322 of 434 LDLR variants currently classified as variants of uncertain significance, conflicting, or absent from ClinVar appear to meet evidence thresholds for reclassification and can be prioritized for expert review, substantially expanding the pool of actionable variant classifications. The screen also reveals a cluster of gain-of-function variants in LDLR class A repeat 5, at least some of which enhance LDL-C uptake through increased apolipoprotein B interaction, with implications for therapeutic genome editing. Last, prime editing uniquely detects splice-altering coding variants missed by cDNA-based screens and pathogenicity predictors, revealing an advantage of endogenous variant installation. CONCLUSIONS: Altogether, activity-normalized prime editing provides a scalable framework for LDLR variant classification that substantially expands the proportion of variants with evidence for genetic diagnosis and reveals novel biology with therapeutic relevance.
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Adenosine deaminases that acts on RNA (ADARs) are RNA-editing enzymes that convert adenosine to inosine in double-stranded RNA. This chapter provides a detailed protocol for identifying inosine-containing RNAs. Candidate ADAR substrates are identified by cleaving poly (A)+ RNA specifically after inosine and using differential display to detect cleaved molecules. To confirm the presence of inosine, each individual candidate substrate is amplified by reverse transcriptase polymerase chain reaction (RT-PCR) and the PCR product is directly sequenced. Sites that contain inosine at the RNA level appear as a mixture of adenosine and guanosine in the cDNA. The relative peak areas provide an estimate of the extent of editing at each site.
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