Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “precise 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 217 records · Page 12Linked to original sources
PubMed1989

A program package for self-assessment and examination in biochemistry.

A BASIC program has been developed for self-evaluation and testing of an individual's knowledge of main categories in biochemistry. The computer tests permit sequential or random distribution of items, random distribution of answers in each item at each new run, effective feedback control with the student, use of a program clock to determine different time allowance, precise and quick analysis and grading of student's answer thus saving the time and labour of examiners. Editing, deleting and appending of new items is easily achieved. Information is obtained for verifying the quality of the test itself. Examination versions of tests in ten categories have been combined into an annual computer test in biochemistry.

Algorithms↗
PubMed2002

Cysteine activation is an inherent in vitro property of prolyl-tRNA synthetases.

Aminoacyl-tRNA synthetases are well known for their remarkable precision in substrate selection during aminoacyl-tRNA formation. Some synthetases enhance the accuracy of this process by editing mechanisms that lead to hydrolysis of incorrectly activated and/or charged amino acids. Prolyl-tRNA synthetases (ProRSs) can be divided into two structurally divergent groups, archaeal-type and bacterial-type enzymes. A striking difference between these groups is the presence of an insertion domain (approximately 180 amino acids) in the bacterial-type ProRS. Because the archaeal-type ProRS enzymes have been shown to recognize cysteine, we tested selected ProRSs from all three domains of life to determine whether cysteine activation is a general property of ProRS. Here we show that cysteine is activated by recombinant ProRS enzymes from the archaea Methanocaldococcus jannaschii and Methanothermobacter thermautotrophicus, from the eukaryote Saccharomyces cerevisiae, and from the bacteria Aquifex aeolicus, Borrelia burgdorferi, Clostridium sticklandii, Cytophaga hutchinsonii, Deinococcus radiodurans, Escherichia coli, Magnetospirillum magnetotacticum, Novosphingobium aromaticivorans, Rhodopseudomonas palustris, and Thermus thermophilus. This non-cognate amino acid was efficiently acylated in vitro onto tRNA(Pro), and the misacylated Cys-tRNA(Pro) was not edited by ProRS. Therefore, ProRS exhibits a natural level of mischarging that is to date unequalled among the aminoacyl-tRNA synthetases.

Amino Acid Sequence↗
PubMed1990

Dryander of Marburg and the first textbook of neuroanatomy.

Born in Wetter, Germany, in 1500, Johannes Eichmann (Dryander) studied medicine and anatomy at the University of Paris from 1528 to 1534. In 1535, he was appointed professor of medicine at the University of Marburg. During the next year he held two public dissections, and in 1536 he was the author of the first text illustrating a Galenic dissection of the human brain. An expanded edition of this early book, the Anatomiae pars prior, was published in 1537. These texts represented an important transition from the dogma of medieval scholasticism to the precise observations of Vesalius. The books depicted the brain in eight figures, with four additional plates describing the skull, skull base, and cranial sutures. Detailed illustrations of the dura mater, cerebral cortex, and posterior fossa structures with clear, but inaccurate, relationship to the cranial nerves demonstrated Dryander's reliance on his own dissections. In 1542, he published a translated edition of Mundinus' anatomy. As was common at that time, the text plagiarized a portion of Vesalius' Tabulae sex, which resulted in the famous anatomist's anger. Despite this, Dryander continued to write on medical subjects as well as mathematics and astrology until his death in 1560. Because he was a progenitor of rational scientific thought, his earlier books represented an important advance in the progression to modern anatomic description and illustration.

Anatomy, Artistic↗
PubMed2006

Unwinding single RNA molecules using helicases involved in eukaryotic translation initiation.

The small (40 S) subunit of the eukaryotic ribosome may have to scan more than 2000 nucleotides (>600 nm) from its 5'cap recruiting point on an mRNA molecule before initiating on a translation start codon. As with many other processes in living cells, including transcription, editing, mRNA splicing, pre-rRNA processing, RNA transport and RNA decay, scanning is facilitated by helicase activity. However, precise quantitative data on the molecular mechanism of scanning, including the roles of helicases, are lacking. Here, we describe a novel atomic force microscopy (AFM)-based procedure to examine the roles of two yeast helicases, eIF4A and Ded1, previously implicated in translation initiation by genetic and biochemical studies. Our results show that eIF4A, especially in the presence of its "cofactor" eIF4B, promotes ATP-dependent unwinding of localised secondary structure in long RNA molecules under tensional loading, albeit only at high protein:RNA ratios. Thus eIF4A can act to separate only a limited number of base-pairs, possibly via a steric unwinding mechanism. In contrast, Ded1 is more effective in reducing (by up to 50 pN at an AFM loading rate of 14 nNs(-1)) the force necessary to disrupt an RNA stem-loop, and thus shows significant kinetic competence to facilitate fast unwinding. These single molecule experiments indicate that Ded1 is likely to act as the more potent unwinding factor on natural mRNA substrates.

Adenosine Triphosphatases↗
PubMed1986

Programs to produce high quality dichotic tapes for central auditory testing.

Dichotic stimulation, the simultaneous presentation of two different acoustic signals to the right and left ears, respectively, is used routinely in the clinical assessment of speech lateralization as well as in other central auditory testing procedures in the clinic and laboratory. At present, most researchers and clinicians depend on a few commercial sources for dichotic tapes, because there are a limited number of facilities which are able to produce such tapes. Moreover, some of the commercial tapes currently offered for sale contain important stimulus errors. In the present paper, we describe a general set of programs for the PDP 11 series of computers, which permits sequences of dichotic stimuli to be generated and output with a high degree of precision. These programs therefore allow researchers to generate any desired sequence of dichotic stimulation, for recording and taping, for use in their research. The programs operate in two stages to generate the required dichotic sequences. In the first stage, the constrained random ordering of the stimuli is generated as specified by the user. In the second stage, after the preliminary stimulus preparation has been completed (for example, using a waveform editing package; cf., D.G. Jamieson and D. A. Naugler, Comput. Biomed. Res., 1985, 18, 480), an audio tape is generated with stimuli presented dichotically, with timing and sequencing precisely as specified.

Auditory Cortex↗
PubMed1982

DSM-III style diagnoses of the episodic disorders.

The episodic disorders can be clearly differentiated from schizophrenia as now rigorously defined in Diagnostic and Statistical Manual of Mental Disorders, 3rd Edition. Because the affective disorder is a more heterogeneous one, the boundaries between this group and episodic disorders is less precise, but this boundary could be clarified with a rigorous definition of the affective disorders comparable to that utilized for schizophrenia. The acute mode of onset and the remitting course are the most useful differentiating features between schizophrenia and the episodic disorder. The presence of toxic or other organic symptoms, including clouding of sensorium, illusions, visual hallucinations, formes frustes of epilepsy, childhood history of minimal brain dysfunction or attentional deficits, and soft neurological signs, aid in differentiating the episodic disorders from manic and depressive episodes. There is a subgroup of episodic disorders that can be differentiated from the epileptoid or organic episodic disorders as well as from the major psychoses by psychodynamic factors alone.

Attention Deficit Disorder with Hyperactivity↗
PubMed1998

Delirium in the elderly. Optimal management.

Delirium is common, morbid and costly, especially among hospitalised elderly patients. Nonetheless, it remains under-recognised and often poorly managed. This article summarises the 5 key steps in the optimal management of delirium. The first step is to precisely define the syndrome of delirium, using key features described in the Diagnostic and Statistical Manual of Mental Disorders (fourth edition) [DSM-IV] or the Confusion Assessment Method. Key features include an acute onset of mental status change, fluctuating course, the presence of inattention, and either disorganised thinking or an altered level of of consciousness. The second step involves the identification of patients at high risk of delirium before it develops, so that preventive measures can be implemented. Risk factors for delirium include advanced age, dementia, impaired functional status, chronic comorbidities and medications, and the severity of the acute illness or surgery. The third step is improved recognition of delirium. Very often, the presence of delirium is neither diagnosed nor properly documented in the medical record. The fourth step is to appropriately evaluate the delirious patient to assess all important contributors to the syndrome. This evaluation will usually involve a careful history, medication review, physical examination and selected laboratory testing. The fifth, and most important, step is the management of the delirious patient. The key elements of management are treating the primary condition(s) leading to delirium, removing all treatable contributing factors, maintaining behavioural control, and supporting the patient and their family.

Aged↗
PubMed1994

Human ventricular tachycardia: precise intraoperative localization with potential distribution mapping.

Electrophysiologically guided operations for ventricular tachycardia (VT) have been directed exclusively by activation time maps. Even with computer-assisted mapping, extensive editing is required, which prolongs the duration of the operation and which may introduce significant error. In contrast, potential distribution maps can be constructed in less than 3 minutes and can be viewed as a movie of developing and receding potentials. In 4 patients undergoing operation for VT, endocardial mapping was performed using form-fitting electrodes containing 160 points. A computerized mapping system, capable of simultaneously recording 256 channels of data, was used to analyze data and to display potential distribution maps sequentially at 1-millisecond intervals as a color movie. A total of eight morphologies of sustained VT were mapped. The mean VT cycle length was 340 +/- 40 milliseconds (range, 274 to 394 milliseconds). In 3 patients with ischemic heart disease, four VT morphologies originated from the subendocardium. All were successfully ablated with cryoablation alone or in conjunction with aneurysmectomy and endocardial resection. A fourth patient with VT secondary to cardiomyopathy had multiple morphologies and received an implantable cardioverter defibrillator. Potential distribution maps correlated well with the concomitant activation time maps. Thus, potential distribution mapping provides a rapid and accurate means of identifying the site of origin of VT facilitating intraoperative mapping in patients undergoing surgical ablation.

Action Potentials↗
PubMed2006

RNA regulation and cancer development.

Cancer is viewed as a genetic disease. According to the currently accepted model of carcinogenesis, several consequential mutations in oncogenes or tumor suppressor genes are necessary for cancer development. In this model, mutated DNA sequence is transcribed to mRNA that is finally translated into functionally aberrant protein. mRNA is viewed solely as an intermediate between DNA (with 'coding' potential) and protein (with 'executive' function). However, recent findings suggest that (m)RNA is actively regulated by a variety of processes including nonsense-mediated decay, alternative splicing, RNA editing or RNA interference. Moreover, RNA molecules can regulate a variety of cellular functions through interactions with RNA, DNA as well as protein molecules. Although, the precise contribution of RNA molecules by themselves and RNA-regulated processes on cancer development is currently unknown, recent data suggest their important role in carcinogenesis. Here, we summarize recent knowledge on RNA-related processes and discuss their potential role in cancer development.

Alternative Splicing↗
PubMedDate not supplied

An independent AGREE evaluation of the Occupational Medicine Practice Guidelines.

BACKGROUND AND CONTEXT: A large number of practice guidelines are being produced by numerous organizations. Health-care professionals need to critically evaluate these practice guidelines to understand whether they are well constructed and representative of the preponderance of evidence. The guideline development process should be precise and rigorous to ensure that the results are reproducible and not vague. PURPOSE: To evaluate the quality of the second edition of the practice guidelines published by the American College of Occupational and Environmental Medicine (ACOEM Guidelines). STUDY DESIGN/SETTING: Four appraisers used the AGREE (Appraisal of Guidelines Research and Evaluation) guideline evaluation instrument to evaluate the ACOEM Guidelines. METHODS: The Guidelines were evaluated with the AGREE guideline evaluation instrument. The AGREE instrument has been widely adopted around the world, and the authors recommended that it be adopted as the standard of guideline construction process evaluation in the United States. The instrument standardizes the quantitative assessment of quality for a guideline's development process across six domains that include: scope and purpose, stakeholder involvement, rigor of development, clarity and presentation, application, and editorial independence. Scores from four assessors were collected and interpreted. Additionally, each evaluator selected one of four global assessment choices: "strongly recommended for use in practice," "recommended for use with some modification or proviso," "not recommended as suitable for use in practice," or "unsure". RESULTS: The ACOEM Guidelines scored highest in the dimensions that evaluated reporting of the guideline's scope and purpose (79.63) as well as clarity and presentation (86.81). The guideline scored much lower in the remaining areas that included stakeholder involvement (46.06), rigor of development (26.59), application (31.48), and editorial independence (19.17). The global assessment was unanimous with all four evaluators assessing the guideline as recommend with proviso. CONCLUSIONS: Many of the Guidelines recommendations were consistent with current literature and guidelines; however, the AGREE assessment instrument evaluates the guideline development process and not the content. All the evaluators thought the content of the guidelines was substantially better than the documentation of the guideline construction process. The ACOEM Guidelines appear to have content consistent with their stated objectives, but the reporting of the guidelines construction process, particularly the rigor of recommendation development, is flawed, and the recommendations may not be valid owing to possible evidence selection deficiencies. The reader should consider these flaws and limitations when using the guideline. The reader should consider utilizing guidelines of higher quality when possible. Future guidelines should incorporate better reporting and give closer attention to guideline construction.

Attitude of Health Personnel↗
PubMed1990

Methodology of ECG interpretation in the Lyon program.

To provide an in-depth interpretation of the spatial QRS-T contour, we established a set of vectorcardiographic parameters computed octant by octant. For each statement the criteria constitute a model which is closely related to pathophysiological patterns. The diagnostic strategy is of the heuristic type. For each diagnosis a table lists several criteria providing both specific and differential diagnostic information. Inter-table competition is handled by specific logic. The program classifies diagnoses according to the number of non-satisfied criteria. Three versions are available including 124, 51 and 7 diagnoses, respectively. The first, intended for interpretation of complex situations, has given satisfactory results in such situations. Rhythm analysis is performed from 8-second recordings. All functions--acquisition, quality control, choice of a dominant complex, wave recognition, parameter extraction, interpretation, editing, storage--are integrated into a mobile cart. A complementary program performs serial analysis of successive tracings. It highlights with great precision morphological changes in the spatial loops and interval variations.

Diagnosis, Computer-Assisted↗
PubMed2025

Engineered virus-like particle-assembled Vegfa-targeting Cas9 ribonucleoprotein treatment alleviates neovascularization in wet age-related macular degeneration.

BACKGROUND: Age-related macular degeneration, particularly the wet form, is a leading cause of vision loss, characterized by vascular endothelial growth factor A (VEGFA) overproduction. Engineered virus-like particles (eVLPs) combine the efficiency of viral systems with the transient nature of non-viral platforms to offer a potential solution for delivering VEGFA-targeting genome editing enzymes in a safe and efficient manner. Here, we investigate the therapeutic efficacy of eVLPs for transient delivery of Vegfa-targeting Cas9 ribonucleoprotein in a laser-induced choroidal neovascularization mouse model of wet age-related macular degeneration. RESULTS: We find that Cas9-eVLPs enables efficient intracellular delivery in vitro, achieving up to 99% insertion and deletion frequency at Vegfa target locus and significant VEGFA protein downregulation in NIH/3T3 cells. A single subretinal injection of Cas9-eVLPs into the mouse retinal pigment epithelium effectively disrupts Vegfa expression, achieving an average indel efficiency of 16.7%. Compared to control groups, the laser-induced choroidal neovascularization mouse model exhibits significantly reduced choroidal neovascularization formation following Cas9-eVLPs intervention, and decreased VEGFA protein levels are detected in the retinal pigment epithelium. Furthermore, the retinal anatomical and functional toxicity are not affected after treatment. CONCLUSIONS: eVLPs exhibit the potential as a safe and efficient delivery platform for Cas9 ribonucleoproteins, achieving precise Vegfa downregulation and significant reduction in choroidal neovascularization in a mouse model of wet age-related macular degeneration. With transient delivery of gene editing enzymes, high editing efficiency, and minimal risk of genomic integration, eVLPs present a promising alternative to conventional delivery systems for advancing genome editing therapies in retinal diseases.

CRISPR-Associated Protein 9↗
PubMed1997

The mechanism of U insertion/deletion RNA editing in kinetoplastid mitochondria.

Recent advances in in vitrosystems and identification of putative enzymatic activities have led to the acceptance of a modified 'enzyme cascade' model for U insertion/deletion RNA editing in kinetoplastid mitochondria. Models involving the transfer of uridines (Us) from the 3'-end of gRNA to the editing site appear to be untenable. Two types of in vitrosystems have been reported: (i) a gRNA-independent U insertion activity that is dependent on the secondary structure of the mRNA; (ii) a gRNA-dependent U insertion activity that requires addition of a gRNA that can form an anchor duplex with the pre-edited mRNA and which contains guiding A and G nucleotides to base pair with the added Us. In the case of the gRNA-mediated reaction, the precise site of cleavage is at the end of the gRNA-mRNA anchor duplex, as predicted by the original model. The model has been modified to include the addition of multiple Us to the 3'-end of the 5'-cleavage fragment, followed by the formation of base pairs with the guiding nucleotides and trimming back of the single-stranded oligo(U) 3'-overhang. The two fragments, which are held together by the gRNA 'splint', are then ligated. Circumstantial in vitroevidence for involvement of an RNA ligase and an endoribonuclease, which are components of a 20S complex, was obtained. Efforts are underway in several laboratories to isolate and characterize specific components of the editing machinery.

Animals↗
PubMed2005

Precise and parallel characterization of coding polymorphisms, alternative splicing, and modifications in human proteins by mass spectrometry.

The human proteome is a highly complex extension of the genome wherein a single gene often produces distinct protein forms due to alternative splicing, RNA editing, polymorphisms, and posttranslational modifications. Such biological variation compounded by the high sequence identity within gene families currently overwhelms the complete and routine characterization of mammalian proteins by MS. A new data base of human proteins (and their possible variants) was created and searched using tandem mass spectrometric data from intact proteins. This first application of top down MS/MS to wild-type human proteins demonstrates both gene-specific identification and the unambiguous characterization of multifaceted mass shifts (Deltam values). Such Deltam values found from the precise identification of 45 protein forms from HeLa cells reveal 34 coding single nucleotide polymorphisms, two protein forms from alternative splicing, and 12 diverse modifications (not including simple N-terminal processing), including a previously unknown phosphorylation at 10% occupancy. Automated protein identification was achieved with a median expectation value of 10(-13) and often occurred simultaneously with dissection of diverse sources of protein variability as they occur in combination. Top down MS therefore has a bright future for enabling precise annotation of gene products expressed from the human genome by non-mass spectrometrists.

Alternative Splicing↗
PubMed2006

Autopathography and depression: describing the 'despair beyond despair'.

The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, emphasizes diagnosis and statistically significant commonalities in mental disorders. As stated in the Introduction, "[i]t must be admitted that no definition adequately specifies precise boundaries for the concept of 'mental disorder' " (DSM-IV, 1994, xxi). Further, "[t]he clinician using DSM-IV should ... consider that individuals sharing a diagnosis are likely to be heterogeneous, even in regard to the defining features of the diagnosis, and that boundary cases will be difficult to diagnose in any but a probabilistic fashion" (DSM-IV, 1994, xxii). This article proposes that it may be helpful for clinicians to study narratives of illness which emphasize this heterogeneity over statistically significant symptoms. This paper examines the recorded experiences of unusually articulate sufferers of the disorder classified as Major Depression. Although sharing a diagnosis, Hemingway, Fitzgerald, and Styron demonstrated different understandings of their illness and its symptoms and experienced different resolutions, which may have had something to do with the differing meanings they made of it. I have proposed a word, autopathography, to describe a type of literature in which the author's illness is the primary lens through which the narrative is filtered. This word is an augmentation of an existing word, pathography, which The Oxford English Dictionary, Second Edition, defines as "a) [t]he, or a, description of a disease," and "b) [t]he, or a, study of the life and character of an individual or community as influenced by a disease." The second definition is the one that I find relevant and which I feel may be helpful to clinicians in broadening their understanding of the patient's experience.

Alcoholism↗
PubMed2026

Engineering the efficient Exo-Cas12i2 for MITE manipulation in rice.

Exo-Cas12i2 v1, a fusion of the 5' exonucleases T5E and PapE, facilitates editing of TA-rich regions and mediates deletions of large genomic fragments. Exo-Cas12i2 v1-driven MITE manipulation enables precise regulation of genes involved in gibberellin-mediated cell elongation and root ethylene responses to generate favorable agronomic traits.

Oryza↗
PubMed1989

[Informatics: applications in bacteriology].

The subject of this work is to describe one of the possible applications of the informatics system in medical bacteriology, its exploitation in edition of the analysis results and in the management of produced stocks. The informatics is presently a very productive tool giving a precise information, a very important time gain and a better control of the costs. This work admit two chapters. In the first one, we give general notions of informatics and in the second one we describe the applications.

Algeria↗
PubMed2025

Innovative strategies for mitochondrial dysfunction in myeloproliferative neoplasms a step toward precision medicine.

Myeloproliferative neoplasms (MPNs) are clonal disorders of hematopoietic stem cells characterized by aberrant proliferation of myeloid lineages, driven primarily by mutations in JAK2, CALR, and myeloproliferative leukemia, leading to constitutive activation of the JAK-STAT pathway. Emerging evidence highlights mitochondrial dysfunction as a key factor in MPN pathogenesis, contributing to increased reactive oxygen species production, mitochondrial DNA mutations, and dysregulated mitochondrial dynamics, which collectively promote clonal expansion and apoptosis resistance. Targeting mitochondrial pathways has gained attention as a therapeutic strategy, with approaches including mitochondria-targeted antioxidants, metabolic inhibitors, and modulation of mitophagy and mitochondrial fission/fusion dynamics. However, challenges such as drug delivery specificity, therapeutic resistance, and off-target effects remain significant. Recent advances in precision medicine, incorporating genomic, transcriptomic, and proteomic profiling, offer a more personalized approach to MPN treatment by tailoring interventions to individual mutation patterns. Additionally, novel therapeutic strategies, including gene editing technologies, RNA-based therapies, and nanoparticle-mediated drug delivery systems, hold promise for overcoming current treatment limitations. The integration of artificial intelligence in drug discovery and biomarker identification further enhances the potential for targeted therapies. Future research should focus on refining these strategies, developing reliable biomarkers for patient stratification, and exploring combination therapies that enhance treatment efficacy while minimizing adverse effects. By addressing mitochondrial dysfunction as an underlying driver of MPNs, these emerging approaches have the potential to improve disease management, extend patient survival, and enhance quality of life. Also, this new approach of precision medicine allows patient stratification and ensures that treatments are formed according to the individual disease biology of each patient, which results in overall better outcomes.

combination drug therapy↗