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At least 73 records · Page 4Linked to original sources
PubMed2000

Interactive construction of residue-based diagrams of proteins: the RbDe web service.

We announce the Residue-based Diagram Editor (RbDe) web service that allows online construction of residue-based diagrams and the creation of stored diagram libraries. The service has been tuned for the construction of snake-like diagrams (for transmembrane proteins) but can be used to render any protein for which defined secondary structure data or hypotheses are available. RbDe is freely available through the Internet from our web site: http://transport.physbio. mssm.edu/rbde/RbDe.html. Licenses for intranet uses can be obtained upon request.

Amino Acid Sequence↗
PubMed2025

Design of highly functional genome editors by modelling CRISPR-Cas sequences.

Gene editing has the potential to solve fundamental challenges in agriculture, biotechnology and human health. CRISPR-based gene editors derived from microorganisms, although powerful, often show notable functional tradeoffs when ported into non-native environments, such as human cells1. Artificial-intelligence-enabled design provides a powerful alternative with the potential to bypass evolutionary constraints and generate editors with optimal properties. Here, using large language models2 trained on biological diversity at scale, we demonstrate successful precision editing of the human genome with a programmable gene editor designed with artificial intelligence. To achieve this goal, we curated a dataset of more than 1 million CRISPR operons through systematic mining of 26 terabases of assembled genomes and metagenomes. We demonstrate the capacity of our models by generating 4.8× the number of protein clusters across CRISPR-Cas families found in nature and tailoring single-guide RNA sequences for Cas9-like effector proteins. Several of the generated gene editors show comparable or improved activity and specificity relative to SpCas9, the prototypical gene editing effector, while being 400 mutations away in sequence. Finally, we demonstrate that an artificial-intelligence-generated gene editor, denoted as OpenCRISPR-1, exhibits compatibility with base editing. We release OpenCRISPR-1 to facilitate broad, ethical use across research and commercial applications.

CRISPR-Cas Systems↗
PubMed2004

How to avoid the reviewer's axe: one editor's view.

Based on his many years of experience, a JMEMS editor provides guidelines for authors that will, if followed, greatly reduce the risk of a devastatingly negative result from the review process. The premise is that there are certain things that rightfully anger reviewers, and, once angered, the reviewers become both negative and aggressive in their judgments--hence, the imagery of "the reviewer's axe" and how to avoid it.

Authorship↗
PubMed2026

Discovery and Engineering of a Rat Endogenous Retrovirus Reverse Transcriptase for Efficient Prime Editing.

CRISPR-based prime editors (PEs) install precise edits into genomic DNA without generating double-strand breaks. Their editing efficiency is highly dependent on reverse transcriptases (RTs), but efficient RT candidates remain limited. Here, we identified 19 novel active RTs by screening 558 candidates. Among them, RERV-RT, derived from Rattus norvegicus, exhibited the highest activity. Through structure-guided engineering and deep mutational scanning, we developed an optimized variant, enRERV-RT, which outperforms conventional M-MLV-RT-based PE systems by 1.20-fold in mammalian and plant cells, and by 1.88-fold at hard-to-edit loci, while enabling precise multiplex editing of functionally relevant genes. Additionally, we developed a high-throughput platform, TRAP-seq-PE, to systematically evaluate prime editor performance. Across diverse mutation types, we found that PE systems based on enRERV-RT exhibited higher editing efficiencies than those based on M-MLV-RT. Collectively, our work establishes a versatile, high-efficiency PE system, thereby facilitating advances in clinical gene therapy and precise crop breeding.

Animals↗
PubMed2005

Research protocol: EB-GIS4HEALTH UK - foundation evidence base and ontology-based framework of modular, reusable models for UK/NHS health and healthcare GIS applications.

EB-GIS4HEALTH UK aims at building a UK-oriented foundation evidence base and modular conceptual models for GIS applications and programmes in health and healthcare to improve the currently poor GIS state of affairs within the NHS; help the NHS understand and harness the importance of spatial information in the health sector in order to better respond to national health plans, priorities, and requirements; and also foster the much-needed NHS-academia GIS collaboration. The project will focus on diabetes and dental care, which together account for about 11% of the annual NHS budget, and are thus important topics where GIS can help optimising resource utilisation and outcomes. Virtual e-focus groups will ensure all UK/NHS health GIS stakeholders are represented. The models will be built using Protege ontology editor http://protege.stanford.edu/ based on the best evidence pooled in the project's evidence base (from critical literature reviews and e-focus groups). We will disseminate our evidence base, GIS models, and documentation through the project's Web server. The models will be human-readable in different ways to inform NHS GIS implementers, and it will be possible to also use them to generate the necessary template databases (and even to develop "intelligent" health GIS solutions using software agents) for running the modelled applications. Our products and experience in this project will be transferable to address other national health topics based on the same principles. Our ultimate goal is to provide the NHS with practical, vendor-neutral, modular workflow models, and ready-to-use, evidence-based frameworks for developing successful GIS business plans and implementing GIS to address various health issues. NHS organisations adopting such frameworks will achieve a common understanding of spatial data and processes, which will enable them to efficiently and effectively share, compare, and integrate their data silos and results for more informed planning and better outcomes.

Journal Article↗
PubMed2006

Guest editors' introduction: implementing evidence-based mental health practices and performance measures in Massachusetts.

In September 2005, a one day educational forum on implementing evidence-based mental health practices and performance measures in Massachusetts was held at Brandeis University. Factors for successful implementation are reviewed. Papers in this issue cover theory, concrete actions, and best practices that will aid policy makers, providers, and consumers in improving their behavioral health services.

Evidence-Based Medicine↗
PubMed2026

Light-activated CRISPR/dCas9 nanomedicine for programmable control of renal fibrosis.

Renal fibrosis is the final common pathway of progressive chronic kidney disease and is maintained by spatially heterogeneous interactions among injured epithelial cells, activated fibroblasts, immune cells, extracellular matrix remodeling, metabolic stress, and persistent profibrotic transcriptional programs. Current therapies slow renal functional decline but do not directly control the regulatory circuits that stabilize maladaptive repair. Photoresponsive renal nanomedicine offers a potential strategy to add external control to anti-fibrotic intervention by combining kidney-directed delivery with light-gated release or activation of molecular payloads. This review examines the emerging interface between photoresponsive nanomaterials and CRISPR/dCas9-based gene regulation for renal fibrosis, with emphasis on upconversion nanoparticles, photoresponsive polymers, ROS- and pH-responsive matrices, optogenetic switches, and renal-compartment-directed carrier design. We argue that the most defensible therapeutic objective is not permanent genome editing or autonomous organ regeneration, but spatially confined, temporally limited, and reversible regulation of validated fibrotic or protective gene programs using CRISPRa, CRISPRi, or dCas9-based epigenome editors. The review therefore evaluates material requirements, optical-dosimetry constraints, payload architecture, renal biodistribution, target-selection logic, safety risks, and preclinical validation criteria. By defining the engineering and biological conditions required for controlled anti-fibrotic regulation, this framework positions photoresponsive renal nanomedicine as a translationally testable route toward localized modulation of fibrotic cell states rather than an overextended claim of kidney regeneration.

Anti-fibrotic gene regulation↗
PubMed1983

Effects of segment and pause manipulations on the identification of treated stutterers.

This study examined the hypothesis that reading rate affects the identification of treated stutterers. Thirty-two pairs of recorded speech samples, in which one member of the pair was a treated stutterer and the other was a nonstutterer, were available from previous research. Listeners had been able to distinguish readily between the members of these pairs. For each pair of samples, the durations of the treated stutterer's segments and pauses were adjusted to match those of the nonstutterer as closely as possible by means of a computer-based waveform editor. A test tape was prepared that included the 32 original pairs of stimuli, the 32 edited pairs, and 64 pairs of foils. Listeners were required to indicate which member of each pair was the treated stutterer. Analysis of the responses indicated that the listeners' ability to distinguish between talkers was significantly reduced for the edited stimulus pairs. The results imply that the rate used by treated stutterers must be critically evaluated if the goal of therapy is the production of perceptually "normal" speech.

Female↗
PubMed2025

Installation of Dominant-Negative Mutations in FAS and TGFβR2 via Base Editing in Primary T Cells.

Adoptive cell transfer (ACT) of engineered T cells is effective against B-cell malignancies but has faltered against solid tumors due to the immunosuppressive tumor microenvironment (TME). FASL and TGFβ are key mediators of T cell dysfunction in the TME and overexpressing dominant negative (dn) forms of their receptors in T cells increases anti-tumor efficacy in solid tumor models. However, an approach which directly targets the endogenous genes would be more amenable to multiplex editing and reduce competition with WT alleles. Here, we employ base editing (BE) in primary human T cells to install naturally occurring dominant negative FAS and TGFβR2 mutations. In vitro survival and proliferation assays demonstrate that BE T cells are resistant to pro-apoptotic and anti-proliferative effects of FAS and TGFβ signaling. CAR-T cells with BE-installed dn TGFβR2 or dn FAS exhibit improvements in cytotoxicity, while dn TGFβR2 CAR T demonstrate increased persistence and reduced expression of phenotypic markers of exhaustion compared to controls. Moreover, BE-engineered dn CAR T outperform lentiviral-engineered cDNA over expression counterparts in several functional assays. Considering the efficiency of BE and its amenability for multiplex editing, our novel approach lends itself to engineering strategies necessary to overcome T cell dysfunction in solid tumors.

CAR T↗
PubMed2025

New retron systems from environmental bacteria identify triggers of anti-phage defense and expand tools for genome editing.

Retrons are bacterial immune systems that protect a bacterial population against phages by killing infected hosts. Retrons typically comprise a reverse transcriptase (RT), a template noncoding RNA that is partially reverse transcribed into RT-DNA, and a toxic effector. The reverse transcriptase (RT), noncoding RNA, and RT-DNA complex sequester the toxic effector until triggered by phage infection, at which point the toxin is released to induce cell death. Due to their ability to produce single-stranded DNA in vivo, retrons have also been engineered to produce donor templates for genome editing in both prokaryotes and eukaryotes. However, the current repertoire of experimentally characterized retrons is limited, with most retrons sourced from clinical and laboratory strains of bacteria. To better understand retron biology and natural diversity, and to expand the current toolbox of retron-based genome editors, we developed a pipeline to isolate retrons and their bacterial hosts from a variety of environmental samples. Here, we identify seven new retron systems, each isolated from a different host bacterium. We characterize DNA production by these retrons and test their ability to defend against a panel of Escherichia coli phages. We find that two of these retrons are disrupted by other elements, in one case a group II intron and in another a separate defense system, yet both retrons still produce RT-DNA. For two other retrons, we further unravel their mechanism of defense by identifying the phage genes responsible for triggering abortive infection. Finally, we engineer these retrons for genome editing in E. coli, demonstrating their potential use in a biotechnological application.

Gene Editing↗
PubMed2002

Challenges in implementing a knowledge editor for the Arden Syntax: knowledge base maintenance and standardization of database linkages.

CONTEXT: Incorporation of research findings into clinical practice lags behind their dissemination in the medical literature. Arden Syntax is a standard that could be used to encode evidence in a clinical decision support system (CDSS). However, dissemination of knowledge is hampered by lack of standard linkages to clinical databases. OBJECTIVE: To create a knowledge editor that facilitates transfer of knowledge from the medical literature to clinical practice via a CDSS. METHODS: Using a Web browser-based application, we implemented linkages to MEDLINE to permit queries on demand and registration of queries to be executed periodically, with results copied into Arden Medical Logic Modules (MLMs). To facilitate standardization of MLMs, database linkages are encoded using emerging HL7 standards such as a data model (virtual medical record). CONCLUSIONS: A Web-based application can facilitate transfer of knowledge into clinical practice and knowledge base maintenance through periodic queries and deployment of standards for knowledge representation.

Artificial Intelligence↗
PubMed1988

Color graphics representations of large sequences in the GEM environment.

The analytical and descriptive color graphics capabilities (the GEM environment) of the CAGE/GEM(a) software system are described using bacteriophage lambda (48,502 base pairs) and Epstein Barr virus (172,282 base pairs) as examples. Genetics and features, as graphic drawings, and the results of sequence analysis as pseudo-colored representations, are simultaneously displayed at all zooming levels. The present upper limit on sequence size is 5 x 10(5) bases. The overlay editor utility which provides the capability to structure complex sequence associated data and knowledge bases into a manageable color graphics format is also described. Holistic correlations that can be made by the display of bacteriophage lambda and Epstein Barr virus in the GEM environment are also discussed.

Bacteriophage lambda↗
PubMed2006

Scope and geographical distribution of African medical journals active in 2005.

OBJECTIVES: To identify all African medical journals actively publishing in 2005, and to create a geodatabase of these to evaluate and monitor future journal activity. DESIGN: A search was done for relevant African medical journals on electronic databases, library catalogues and internet sites, and a list was compiled of active journals. A survey was conducted via questionnaire of editors of all listed African medical journals defined as having an editorial base on the continent. RESULTS: One hundred and fifty-eight African medical journals were identified, published in 33 countries. One hundred and fifty-three editors were surveyed via email, post and/or fax. There was a 39% response rate from editors based in 17 countries. Fifty-one journals were published in English, 7 in French and 1 in Portuguese. Most journals were owned by an association or a society and were funded from a combination of sources. Journals covered general medical and specialist medical interest equally. Most (41 of 59 journals) had a circulation below 1 000, and most (52/59) published 4 or fewer issues a year. Almost all the journals included original research, and articles were peer reviewed. Few were indexed on Medline (N = 18) and EMBASE (N = 10). Plotting journal location using Geographic Information Systems (GIS) software provided a snapshot view of current journal activity. CONCLUSIONS: This study is likely to represent the most comprehensive list of current African medical journals. It confirms growth in African health care research and journal activity on the continent. Limited inclusion in international databases and accessibility to African researchers remain challenges in achieving publication of high-quality African research in high-quality African journals.

Abstracting and Indexing↗