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PubMed1993

Self-injurious behaviour (SIB)--from definition to human rights.

This article is part of a special section on 'self-injurious behaviour and autism' and is mainly based on a book edited by Luiselli, Matson and Singh (1992) addressing empirical data on self-injurious behaviour and mental retardation from a behavioural perspective. Within the overview of the book some information on autism is also presented and critically discussed. Self-injurious behaviour is a poorly understood phenomenon and problematic in many ways; its definition is not easy; little is known about the causes and neuroscientific models. Demographic data are scarce and functional analysis and interventions (behavioural techniques, medication, education) need to be further developed, under the protection of human rights committees.

Autistic Disorder↗

PubMed2000

RNA editing of the Drosophila para Na(+) channel transcript. Evolutionary conservation and developmental regulation.

Post-transcriptional editing of pre-mRNAs through the action of dsRNA adenosine deaminases results in the modification of particular adenosine (A) residues to inosine (I), which can alter the coding potential of the modified transcripts. We describe here three sites in the para transcript, which encodes the major voltage-activated Na(+) channel polypeptide in Drosophila, where RNA editing occurs. The occurrence of RNA editing at the three sites was found to be developmentally regulated. Editing at two of these sites was also conserved across species between the D. melanogaster and D. virilis. In each case, a highly conserved region was found in the intron downstream of the editing site and this region was shown to be complementary to the region of the exonic editing site. Thus, editing at these sites would appear to involve a mechanism whereby the edited exon forms a base-paired secondary structure with the distant conserved noncoding sequences located in adjacent downstream introns, similar to the mechanism shown for A-to-I RNA editing of mammalian glutamate receptor subunits (GluRs). For the third site, neither RNA editing nor the predicted RNA secondary structures were evolutionarily conserved. Transcripts from transgenic Drosophila expressing a minimal editing site construct for this site were shown to faithfully undergo RNA editing. These results demonstrate that Na(+) channel diversity in Drosophila is increased by RNA editing via a mechanism analogous to that described for transcripts encoding mammalian GluRs.

Alternative Splicing↗

PubMedDate not supplied

[The Italian Society of Nephrology Guidelines (3rd Edition): principles and methods].

Scientific Societies at both a local and international level are making big effort to prepare their clinical practice guidelines. The Italian Society of Nephrology has already published in two previous editions a series of guidelines relating to various aspects of management and diagnosis of different renal diseases. In this review we present the criteria of the 3(rd) edition of the Italian Society of Nephrology guidelines. This 3(rd) edition of guidelines will be based on the availability of scientific evidence in different areas of nephrology, dialysis and transplantation. Ten key intervention questions have been identified, based on the availability of systematic reviews of randomized trials or individual randomized address them. Systematic reviews and randomized trials are the optimal study design to address intervention questions. These have been summarized based upon rigid methodological criteria and strictly reflect the evidence basis. The different phases of development and publication of the 3(rd) edition of the Italian Society of Nephrology guidelines are presented.

Italy↗

PubMed2003

Semiautomated segmentation of blood vessels using ellipse-overlap criteria: method and comparison to manual editing.

Two-dimensional intensity-based methods for the segmentation of blood vessels from computed-tomography-angiography data often result in spurious segments that originate from other objects whose intensity distributions overlap with those of the vessels. When segmented images include spurious segments, additional methods are required to select segments that belong to the target vessels. We describe a method that allows experts to select vessel segments from sequences of segmented images with little effort. Our method uses ellipse-overlap criteria to differentiate between segments that belong to different objects and are separated in plane but are connected in the through-plane direction. To validate our method, we used it to extract vessel regions from volumes that were segmented via analysis of isolabel-contour maps, and showed that the difference between the results of our method and manually-edited results was within inter-expert variability. Although the total editing duration for our method, which included user-interaction and computer processing, exceeded that of manual editing, the extent of user interaction required for our method was about a fifth of that required for manual editing.

Aneurysm↗

PubMed2025

CRISPRoff epigenome editing for programmable gene silencing in human cell lines and primary T cells.

The advent of CRISPR-based technologies has enabled the rapid advancement of programmable gene manipulation in cells, tissues, and whole organisms. An emerging platform for targeted gene perturbation is epigenetic editing, the direct editing of chemical modifications on DNA and histones that ultimately results in repression or activation of the targeted gene. In contrast to CRISPR nucleases, epigenetic editors modulate gene expression without inducing DNA breaks or altering the genomic sequence of host cells. Recently, we developed the CRISPRoff epigenetic editing technology that simultaneously establishes DNA methylation and repressive histone modifications at targeted gene promoters. Transient expression of CRISPRoff and the accompanying single guide RNAs in mammalian cells results in transcriptional repression of targeted genes that is memorized heritably by cells through cell division and differentiation. Here, we describe our protocol for the delivery of CRISPRoff through plasmid DNA transfection, as well as the delivery of CRISPRoff mRNA, into transformed human cell lines and primary immune cells. We also provide guidance on evaluating target gene silencing and highlight key considerations when utilizing CRISPRoff for gene perturbations. Our protocols are broadly applicable to other CRISPR-based epigenetic editing technologies, as programmable genome manipulation tools continue to evolve rapidly.

Humans↗

PubMed2003

Logic-based remodeling of the Digital Anatomist Foundational Model.

This paper describes a development cycle for the engineering of large knowledge bases: A graphical tool is used for editing and the content is transformed into a logic-based representation language. This representation is used to check the consistency of the knowledge base as well as to facilitate the reviewing process. Showing the usefulness of this approach, aspects of the Digital Anatomist Foundational Model will be transformed into a Description Logics representation. We introduce a special modeling technique to account for the representation of the complex part/whole relationships in the biomedical domain.

Anatomy↗

PubMed2003

Developmental co-variation of RNA editing extent of plastid editing sites exhibiting similar cis-elements.

In tobacco, 30 of 34 sites in chloroplast transcripts that undergo C-to-U RNA editing can be grouped into clusters of 2-5 sites based on sequence similarities immediately 5' to the edited C. According to a previous transgenic analysis, overexpression of transcripts representing one cluster member results in reduction in editing of all cluster members, suggesting that members of an individual cluster share a trans-factor that is present in limiting amounts. To compare leaves and roots, we quantified the editing extent at 34 sites in wild-type tobacco and at three sites in spinach and Arabidopsis. We observed that transcripts of most NADH dehydrogenase subunits are edited inefficiently in roots. With few exceptions, members of the same editing site cluster co-varied in editing extent in chloroplasts versus non-green root plastids, with members of most clusters uniformly exhibiting either a high or low editing extent in roots. The start codon of the ndhD transcript must be created by editing, but the C target is edited inefficiently in roots, and no NDH-D protein could be detected upon immunoblotting. Our data are consistent with the hypothesis that cluster-specific trans-factors exist and that some are less abundant in roots, limiting the editing extent of certain sites in root plastids.

Arabidopsis↗

PubMed2026

Endogenous CRISPR-Based Removal of Tetracycline Resistance in Bifidobacterium animalis subsp. lactis Through a Safe-by-Design Approach.

Bifidobacterium animalis subsp. lactis is widely used as a probiotic; however, the presence of the tetracycline resistance gene tetW raises safety and regulatory concerns due to its potential mobility within the gut microbiome. Here, we applied a Safe-by-Design strategy using the endogenous CRISPR-Cas system of B. animalis subsp. lactis BLC01 to inactivate tetW through the introduction of premature stop codons. Whole-genome sequencing confirmed the intended editing and excluded relevant off-target effects. tetW inactivation markedly reduced the tetracycline minimum inhibitory concentration, restoring susceptibility below the tetracycline cut-off value for bifidobacteria (8 μg/mL). Comparative phenotypic analyses demonstrated that the edited strain (BLC01-2F3G10) retained key probiotic traits, including tolerance to acid, bile, and osmotic stress, exopolysaccharide production, aggregation capacity, survival during simulated gastrointestinal digestion and adhesion to intestinal epithelial cells. Importantly, no reversion to tetracycline resistance was observed after prolonged exposure to sub-inhibitory minimal selective antimicrobial concentration, indicating genetic stability of the edited phenotype. Collectively, these findings demonstrate that endogenous CRISPR-based genome editing can be leveraged to selectively remove antimicrobial resistance determinants from probiotic strains while preserving functionality, supporting the development of next-generation probiotics with an improved safety profile and reduced potential for antimicrobial resistance dissemination in the human gut.

Tetracycline Resistance↗

PubMed1990

RNA editing of apolipoprotein B mRNA. Sequence specificity determined by in vitro coupled transcription editing.

Apolipoprotein (apo) B-48 mRNA is produced by in vivo RNA editing which involves a C----U conversion of the first base of the codon CAA for Gln-2153, changing it to UAA, an in-frame stop codon. We have reproduced the editing reaction in vitro using nuclear extracts. Efficient RNA editing was demonstrated by using apoB mRNA segments as substrate or in a coupled transcription-editing reaction using apoB minigenes as template. ApoB minigenes were constructed by ligating the adenovirus major late promoter to a fragment of apoB-100 DNA containing the editing site and used for the transcription-editing reaction. We defined the sequence specificity of the editing reaction using site-specific single and multiple base mutants constructed by the polymerase chain reaction. Among 22 different mutant apoB-100 minigene constructs containing mutations in the bases immediately flanking the edited C-6666, 20 were edited in the coupled transcription-editing reaction. The results suggest a relatively lax sequence specificity for apoB mRNA editing. Our observation may have important implications for apoB-48 biogenesis as well as for the editing process as a general biologic regulatory mechanism.

Animals↗

PubMed2004

The pedigree tool: web-based visualization of a family tree.

We describe the development of a novel tool that facilitates the design and visualization of pedigrees using a special Internet application. The tool is programmed in Java, using a PHP script as an interface. This web-based tool is used to generate, edit, and/or view pedigrees. The advantage of our novel tool is that it is based on a notation that allows the representation of any given number of generations, family members per generation, and multiple clinical or genetic features of an individual family member. In addition, the notation allows us to minimize the storage space by 100% to 500% and to standardize the presentation of family trees and segregation analysis for inheritance of mendelian disorders or even complex traits. This pedigree tool has been implemented with a database of thyroid-stimulating hormone receptor (TSHR) mutations (http://www.uni-leipzig.de/innere/tshr/).

Computer Graphics↗

PubMed2004

Psychiatric diagnoses of infants and toddlers referred to a community mental health system.

There has been increased interest in improving mental health assessment and treatment of young children. However, there are limited data regarding the prevalence of psychiatric disorders among infants and toddlers. The recent development of measures and classification systems that are specific to this age group has enabled researchers to begin to investigate the social, emotional, and behavioral problems of young children. The present study reviews the major research that has been conducted in this area and examines the prevalence of psychiatric diagnoses of infants and toddlers referred to a public community mental health system. The current investigation also compares the frequency of diagnoses of children who have been evaluated based on the Diagnostic and Statistical Manual (4th edition) with another group of children who were diagnosed based on the Diagnostic Classification: 0-3 system. Although there were some differences between the two samples and classification systems, analysis indicated that parent-child relational problems, adjustment difficulties, regulatory problems, and developmental disorders are some of the more common diagnoses prevalent among young children referred for outpatient treatment. As diagnostic measures and classification systems continue to improve, clinicians will have a better understanding of the mental health problems and treatment needs of young children.

Adult↗

PubMed2024

RNA editing in host lncRNAs as potential modulator in SARS-CoV-2 variants-host immune response dynamics.

Both host and viral RNA editing plays a crucial role in host's response to infection, yet our understanding of host RNA editing remains limited. In this study of in-house generated RNA sequencing (RNA-seq) data of 211 hospitalized COVID-19 patients with PreVOC, Delta, and Omicron variants, we observed a significant differential editing frequency and patterns in long non-coding RNAs (lncRNAs), with Delta group displaying lower RNA editing compared to PreVOC/Omicron patients. Notably, multiple transcripts of UGDH-AS1 and NEAT1 exhibited high editing frequencies. Expression of ADAR1/APOBEC3A/APOBEC3G and differential abundance of repeats were possible modulators of differential editing across patient groups. We observed a shift in crucial infection-related pathways wherein the pathways were downregulated in Delta compared to PreVOC and Omicron. Our genomics-based evidence suggests that lncRNA editing influences stability, miRNA binding, and expression of both lncRNA and target genes. Overall, the study highlights the role of lncRNAs and how editing within host lncRNAs modulates the disease severity.

Biological sciences↗

PubMed1995

Deamination of mammalian glutamate receptor RNA by Xenopus dsRNA adenosine deaminase: similarities to in vivo RNA editing.

Double-stranded RNA (dsRNA) adenosine deaminase (dsRAD) converts adenosines to inosines within dsRNA. A great deal of evidence suggests that dsRAD or a related enzyme edits mammalian glutamate receptor mRNA in vivo. Here we map the deamination sites that occur in a truncated glutamate receptor-B (gluR-B) mRNA after incubation with pure Xenopus dsRAD. We find remarkable similarities, as well as distinct differences, between the observed deamination sites and the sites reported to be edited within RNAs isolated from mammalian brain. For example, although deamination at the biologically relevant Q/R editing site occurs, it occurs much less frequently than editing at this site in vivo. We hypothesize that the similarities between the deamination and editing patterns exist because the deamination specificity that is intrinsic to dsRAD is involved in selecting editing sites in vivo. We propose that the observed differences are due to the absence of accessory factors that play indirect roles in vivo, such as binding to and occluding certain sites from dsRAD, or promoting the RNA structure required for correct and efficient editing. The work reported here also suggests that dsRAD is capable of much more selectivity than previously thought; a minimal number of deamination sites (average < or = 5) were found in each gluR-B RNA. We speculate that the observed selectivity is due to the various structural elements (mismatches, bulges, loops) that periodically interrupt the base paired region required for editing.

Adenosine Deaminase↗

PubMed1994

Developmental regulation of RNA editing and polyadenylation in four life cycle stages of Trypanosoma congolense.

The accumulation of many edited mRNAs is developmentally regulated in a transcript-specific fashion in Trypanosoma brucei. In addition, these transcripts are frequently present in two size classes which differ substantially in the lengths of their poly(A) tails, and poly(A) tail length is also developmentally regulated. Previously, these phenomena have only been studied in the mammalian bloodstream and insect procyclic forms (BF and PF, respectively) of T. brucei. In this paper, we examine developmental regulation of edited RNA abundance and poly(A) tail length of 3 mitochondrially encoded RNAs in mammalian BF and 3 insect stages (PF, epimastigotes, and metacyclics) of T. congolense. T. congolense BF and PF are similar, but not identical, to these stages of T. brucei with regard to edited RNA accumulation and poly(A) tail length. At the level of edited RNA, both epimastigotes and metacyclic stage parasites appear to be pre-adapted for the respiratory mechanisms of BF but not yet down-regulated from the cytochrome-based respiration of PF since edited RNAs encoding NADH dehydrogenase components are up-regulated and edited CYb RNA is abundant in these stages. Poly(A) tail lengths of mitochondrial mRNAs appear to be regulated independently of edited RNA abundance. These results indicate that multiple mechanisms for regulation of mitochondrial gene expression are active throughout the trypanosome life cycle.

Animals↗

PubMed1999

Kinetoplastid RNA editing does not require the terminal 3' hydroxyl of guide RNA, but modifications to the guide RNA terminus can inhibit in vitro U insertion.

During RNA editing in kinetoplastid parasites, trans-acting guide RNAs (gRNAs) direct the insertion and deletion of U residues at precise sites in mitochondrial pre-mRNAs. We show here that some modifications to the 3' terminal ribose of gRNA inhibit its ability to direct in vitro U insertion. However, we found that gRNAs lacking this moiety in some circumstances support in vitro editing. Thus, the 3' OH is not required. Inhibition resulting from gRNA modification can be overcome by increasing the gRNA-pre-mRNA base-pairing potential upstream of the editing site, suggesting an importance for this interaction to productive processing.

Animals↗

PubMed2026

Characterization and comparative analysis of the complete mitochondrial genome sequence of Aucklandia lappa Decne.

BACKGROUND: Aucklandia lappa Decne, a precious medicinal herb in China, utilises the dried rhizome as its medicinal part, which riches in volatile oils, sesquiterpene compounds and other active constituents. Although the mitogenome of A. lappa has been assembled, related research remains in its preliminary stages, far from achieving comprehensive and in-depth understanding. RESULTS: In this paper, the complete mitogenome of A. lappa was assembled by employing a hybrid strategy that combined Illumina short-read and Nanopore long-read sequencing. The assembled mitogenome is 436,648 bp in size with a GC content of 45.06%. The mitogenome has only one chromosomal structure, It contains 54 genes, including 31 protein-coding genes(PCG), 19 tRNA genes, and 4 rRNA genes. A total of 32 high-frequency codons exhibiting significant AT-bias, 431 RNA editing sites, and 26 homologous fragments were transferred from the chloroplast to mitochondria genes (7,337 bp, 1.68%). Furthermore, we conducted a phylogenetic analysis involving in A. lappa and 27 other taxa to clarify its evolutionary and taxonomic status. These findings provide a foundation for further understanding the evolutionary relationships within Asteraceae plant. CONCLUSION: Through the assembly and comprehensive analysis of A. lappa mitogenome, This study has for the first time fully elucidated its mitogenomic structural characteristics.These results not only provide high-quality genetic resources for research on the Asteraceae mitogenome but also lay a solid foundation for in-depth exploration of the evolution and functional genomics of medicinal plants in the Asteraceae family.

Genome, Mitochondrial↗

PubMed1997

Extensive RNA editing and possible double-stranded structures determining editing sites in the atpB transcripts of hornwort chloroplasts.

Three nonsense codons and an unusual initiation codon were located within the putative coding region of the atpB gene of chloroplast DNA of the hornwort Anthoceros formosae. Nucleotide sequencing of cDNA prepared from transcripts revealed extensive RNA editing. The unusual initiation codon ACG was changed to AUG and three nonsense codons were converted into sense codons. In total 15 C residues of the genomic DNA were replaced by U residues in the mRNA sequences, while 14 U residues were replaced by C residues. This is the highest number of editing events for a chloroplast mRNA reported so far. Partial editing was also shown in a cDNA clone where 23 sites were edited but six sites remained unedited, representing the existence of premature mRNA. The expected two-dimensional structure of the mRNA shows the existence of a sequence complementary to every editing site, which can produce continuous base pairing longer than 5 bp, suggesting that mispairing in the double strand is the site determinant for RNA editing in Anthoceros chloroplasts. Comparison of the cDNA sequence with other chloroplast genes suggests that the mechanism arose in the first land plants and has been reduced during evolution.

Amino Acid Sequence↗

PubMed1998

Recent advances in mammalian RNA editing.

RNA editing is a posttranscriptional modification that results in the generation of nucleotides within an RNA transcript that do not match the bases present within the genome. Mammalian RNA editing events, often represented by cytidine-to-uridine and adenosine-to-inosine conversions, are predominantly mediated by base deamination. In the past decade, important advances have been made in the understanding of editing mechanisms, the identification of RNA sequences and structures necessary for editing regulation, and the cloning and characterization of editing enzymes. It has also recently been appreciated that RNA editing within mammalian substrates can have profound functional consequences in protein function, implicating this posttranscriptional modification as important in the production of molecular diversity.

Adenosine Deaminase↗