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Articles by David Taylor
A cryptic binding pocket regulates the metal-dependent activity of Cas9
Abstract Cas9 is a metal-dependent nuclease used for genome editing across diverse cells and organisms exhibiting distinct ionic environments, yet how metal ions regulate its catalytic function, and consequently its editing efficiency remains unclear. Here, molecular simulations, Markov state models, and mixed quantum–classical approaches reveal that divalent metals promote activation of the catalytic HNH domain through formation of a divalent metal-binding pocket (DBP) at the HNH–RuvC interface.
Architecture of a DNA-guided Cas12a
Abstract CRISPR–Cas systems have largely been restricted to RNA-guided nucleases. Here, we present the cryo-electron microscopy structure of Acidaminococcus sp. Cas12a bound to a pseudo-DNA (ΨDNA) guide and RNA target, revealing how Cas12a can accomplish DNA-guided RNA recognition. The ΨDNA hairpin bridges the recognition and nuclease lobes, mimicking a PAM-proximal duplex and positioning the spacer to allow formation of a canonical RNA–DNA heteroduplex along the recognition lobe.
Nested Carbon Governance in Southeast Asia: Towards Just Nature-Based Solutions?
1 Introduction Discussions centred on Nature-based Solutions (NbS) have progressed and diversified since the concept's introduction almost two decades ago (Albert et al. 2021; Sowińska-Świerkosz and García 2022). As “solutions to societal challenges that involve working with nature” (Seddon et al. 2021: 1519), NbS aim to provide “benefits for both human well-being and biodiversity” (Seddon 2022: 1410), which include climate change mitigation and adaptation measures.
Phage-encoded factor stimulates DNA degradation by the Hna anti-phage defense system
Abstract Prokaryotic organisms have evolved unique strategies to acquire immunity against the constant threat of bacteriophage (phage) and mobile genetic elements. Hna is a broadly distributed anti-phage immune system that confers resistance against diverse phage by eliciting an abortive infection response.
Molecular mechanisms and biotechnology applications of CRISPR–Cas12a
Abstract CRISPR–Cas12a is a versatile RNA-guided nuclease that has rapidly gained prominence for its dual functionality in genome editing and nucleic acid detection. In this Review, we discuss the structural, biochemical and mechanistic features of Cas12a that underpin its autonomous processing of the guide RNA and indiscriminate cleavage of single-stranded DNA, which enable Cas12a applications ranging from gene therapy to rapid diagnostics.
Comparative characterization of Cas12f orthologs reveals mechanistic features underlying enhanced genome editing efficiency
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Abstract Miniature CRISPR–Cas12f nucleases are attractive candidates for therapeutic genome editing because of their compact size and compatibility with adeno-associated virus (AAV) delivery. However, editing efficiencies in mammalian cells are lower than those of larger systems. The extensive phylogenetic diversity of Cas12f suggests unexplored mechanistic variation with the potential for optimization.
By Kaoling Guan, Rodrigo Fregoso Ocampo, Cindy J. Castelle, Dominic T. Castanzo, Nicole Thomas, Molly Brothers, Tyler L Dangerfield, Matthew Hooper, Madeline West, Nathan M Appleby, Lisa Alexander, Kenneth Johnson, Christopher Brown, David Taylor, Paula B. Matheus Carnevali, Liliana Gonzalez-Osorio, Isabella Krudop, Rebecca C. Lamothe, Daniela S. Aliaga Goltsman, Cristina N. Butterfield
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Nature
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Theoretical and Practical Implications Derived From the Formulation of the Theory of Critical Distances
1 Introduction The presence of notches in structural parts is a very common phenomenon. Actually, there are frequent situations where the existing defects endangering the structural integrity of the corresponding component are not crack-like defects (i.e., infinitely sharp defects). Examples are mechanical damage, corrosion defects, pores or fabrication defects (among others), and drilled holes and slots.
Special feature on antipsychotic discontinuation in schizophrenia - Schizophrenia
More than 70 years after the first use of chlorpromazine in psychosis, there remain widely different views on the prescribing of antipsychotic drugs in schizophrenia and schizoaffective disorder. While most practitioners recognise the need for long-term treatment, there is an incomplete consensus on the optimal duration of treatment, although most people with schizophrenia-like psychoses are prescribed antipsychotics for the whole of their lives, after diagnosis.
Economic evaluation of different haematological monitoring schemes for patients with treatment-resistant schizophrenia using clozapine
Clozapine is considered the most effective treatment option for patients with treatment-resistant schizophrenia (TRS). Reference Siskind, McCartney, Goldschlager and Kisely1 Patients experience a persistence of significant symptoms despite prior adequate pharmacological treatment with at least two non-clozapine antipsychotic drugs.
Visualization of a multi-turnover Cas9 after product release - Nature Communications
Abstract While the most widely used CRISPR-Cas enzyme is the Cas9 endonuclease from Streptococcus pyogenes (Cas9), it exhibits single-turnover enzyme kinetics which leads to long residence times on product DNA. This blocks access to DNA repair machinery and acts as a major bottleneck during CRISPR-Cas9 gene editing.
Co‐transformation using T‐DNA genes from Agrobacterium strain 82.139 enhances regeneration of transgenic shoots in Populus
Introduction Genetic engineering and gene editing are powerful tools for the manipulation of agronomic traits (Cardi et al., 2023). Current gene editing methods in plants most frequently use conventional transgenesis to insert CRISPR/Cas components into the genome, but it is difficult or impossible in the vast majority of species or genotypes outside of model systems (Atkins and Voytas, 2020; Chen et al., 2019).
Seaweed aquaculture research in New Zealand: current advances, benefits, challenges, and perspectives
Seaweed aquaculture is one of the fastest growing aquaculture sectors globally, with algal production (mostly seaweed and some microalgae) nearly tripling over the past two decades to reaching 36.5 million tonnes of wet weight, worth USD 17 billion in 2022 (FAO Citation2024). While Asian countries still dominate this industry, seaweed aquaculture is expanding worldwide due to the diverse applications and benefits of seaweed and its biomass.
Structural basis for a dual-function type II-B CRISPR-Cas9
Abstract Cas9 from Streptococcus pyogenes (SpCas9) revolutionized genome editing by enabling programmable DNA cleavage guided by an RNA. However, SpCas9 tolerates mismatches in the DNA-RNA duplex, which can lead to deleterious off-target editing. Here, we reveal that Cas9 from Francisella novicida (FnCas9) possesses a unique structural feature, the REC3 clamp, that underlies its intrinsic high-fidelity DNA targeting.
The assembly factor Reh1 is released from the ribosome during its initial round of translation - Nature Communications
Abstract Assembly of functional ribosomal subunits and successfully delivering them to the translating pool is a prerequisite for protein synthesis and cell growth. In S. cerevisiae, the ribosome assembly factor Reh1 binds to pre-60S subunits at a late stage during their cytoplasmic maturation. Previous work shows that the C-terminus of Reh1 inserts into the polypeptide exit tunnel of the pre-60S subunit.
Half of land use carbon emissions in Southeast Asia can be mitigated through peat swamp forest and mangrove conservation and restoration - Nature Communications
Abstract Southeast Asia (SEA) contributes approximately one-third of global land-use change carbon emissions, a substantial yet highly uncertain part of which is from anthropogenically-modified peat swamp forests (PSFs) and mangroves.
Genetic identification of undiagnosed benign ethnic neutropenia in patients receiving clozapine treatment
Published online by Cambridge University Press: 09 December 2024 Helena Aziri [Opens in a new window] , David Taylor [Opens in a new window] Show author details Keywords Benign ethnic neutropeniaclozapinepharmacogenomicsethnicityneutropenia Type Original Article Information The British Journal of Psychiatry , First View , pp.
Visualization of a multi-turnover Cas9 after product release
Abstract While the most widely used CRISPR-Cas enzyme is the S. pyogenes Cas9 endonuclease (Cas9), it exhibits single-turnover enzyme kinetics which leads to long residence times on product DNA. This blocks access to DNA repair machinery and acts as a major bottleneck during CRISPR-Cas9 gene editing.
Mechanism of type II-B CRISPR-Cas9 enhanced specificity
Abstract The Cas9 endonuclease from Streptococcus pyogenes (SpCas9) has revolutionized genome editing, as it can be programmed by an RNA sequence to target and cleave DNA. However, SpCas9 is prone to deleterious off-target effects, prompting efforts to develop and discover high-fidelity variants. In the search for a more precise genome editor, many intrinsically specific Cas9 orthologs have been found in nature.
Engineered PsCas9 enables therapeutic genome editing in mouse liver with lipid nanoparticles - Nature Communications
Abstract Clinical implementation of therapeutic genome editing relies on efficient in vivo delivery and the safety of CRISPR-Cas tools. Previously, we identified PsCas9 as a Type II-B family enzyme capable of editing mouse liver genome upon adenoviral delivery without detectable off-targets and reduced chromosomal translocations. Yet, its efficacy remains insufficient with non-viral delivery, a common challenge for many Cas9 orthologues.
Mortality associated with clozapine: what is the evidence?
It is undeniable that clozapine can lead to fatal outcomes if its toxic effects are not promptly identified and managed. While acknowledging the risks associated with clozapine, media reports can overestimate the number of fatal outcomes due to the drug.
Key benthic species are affected by predicted warming in winter but show resistance to ocean acidification
1 INTRODUCTION The fate of key coastal species is a major concern in changing climate conditions (Cooley et al., 2022; IPCC, 2022; Pörtner et al., 2021). Climate change adds to other anthropogenic stressors, such as habitat modifications, exploitation or pollution, and can intensify their effects on the distribution, functioning and production of marine species (Bowler et al., 2020; Gissi et al., 2021; O'Hara et al., 2021).
Clinical outcomes with paliperidone palmitate 3-monthly injection as monotherapy: observational 3-year follow-up of patients with schizophrenia
Hostname: page-component-7c8c6479df-p566r Total loading time: 0 Render date: 2024-04-03T08:54:45.233Z Has data issue: false hasContentIssue false Published online by Cambridge University Press: 07 March 2024 Ivana Clark [Opens in a new window] , Phoebe Wallman [Opens in a new window] , Siobhan Gee [Opens in a new window] and David Taylor [Opens in a new window] Show author details Keywords continuationlong-actingpaliperidone 3-monthrelapseschizophrenia Type Research Article Information...
Use of Nonhuman Sera as a Highly Cost-Effective Internal Standard for Quantitation of Multiple Human Proteins Using Species-Specific Tryptic Peptides: Applicability in Clinical LC-MS Analyses
SPECIAL ISSUE This article is part of the Women in Proteomics and Metabolomics special issue. The use of liquid chromatography–tandem mass spectrometry (LC-MS/MS) has revolutionized the analysis of certain “small molecule” classes in clinical chemistry. The added specificity of MS detection over immunometric techniques or competitive binding protein assays, coupled with selective sample preparation methods and chromatographic analyses, has been exploited in many clinical laboratories.
Case-based learning: safe withdrawal and tapering of antidepressants
After reading this article, you should be able to: Understand the rationale for tapering antidepressants gradually, in a hyperbolic pattern and a rate titrated to the individual; Counsel a patient on how to undertake a careful, hyperbolic ; Help a patient use different formulations of medication to facilitate this process. It is now recognised that withdrawal effects from antidepressants are more common, and can be more severe and long-lasting than previously understood.
Maternal Nutritional Status and the Microbiome across the Pregnancy and the Post-Partum Period
Abstract : Appropriate nutrition during pregnancy and the post-partum period is vital for both the mothers and their offspring. Both under- and over-nourished status may have important microbial implications on the maternal and infant gut microbiomes. Alterations in the microbiome can have implications for a person’s risk of obesity and metabolic diseases.
International Variation in Clozapine Hematologic Monitoring
International Variation in Clozapine Hematologic Monitoring—A Call for Action Clozapine was first synthesized in the 1950s but remains the only licensed medication for treatment-resistant psychosis.1 Treatment-resistant psychosis, defined as the persistence of psychotic symptoms despite sequential antipsychotic treatment, is a major cause of disability and functional impairment worldwide.1 Within the past decade, there has been a commitment among health institutions to address clozapine...
Point of care assay for blood aripiprazole concentrations: development, validation and utility
Hostname: page-component-546b4f848f-w58md Total loading time: 0 Render date: 2023-05-31T07:17:17.058Z Has data issue: false Feature Flags: { "useRatesEcommerce": true } hasContentIssue false Published online by Cambridge University Press: 31 May 2023 Matthew Atkins [Opens in a new window] , David Taylor [Opens in a new window] , Edward Chesney [Opens in a new window] , Luiz Dratcu [Opens in a new window] and ...Show all authors Show author details Abstract Background The antipsychotic...
What are the barriers and facilitators of clozapine use in early psychosis? A survey of UK early intervention clinicians - Schizophrenia
Abstract Clozapine is the most effective medication for treatment-resistant psychosis, but evidence points to substantial underuse, especially within early intervention psychosis (EIP) services. We explored clinicians’ views on perceived barriers and facilitators to offering patients clozapine within EIP services. A cross-sectional survey was distributed electronically to clinicians practising in EIP services across England.
Does AlphaFold2 model proteins’ intracellular conformations? An experimental test using cross-linking mass spectrometry of endogenous ciliary proteins | Communications Biology
Abstract A major goal in structural biology is to understand protein assemblies in their biologically relevant states. Here, we investigate whether AlphaFold2 structure predictions match native protein conformations.
Bioengineering of Soybean Oil and Its Impact on Agronomic Traits
Abstract : Soybean is a major oil crop and is also a dominant source of nutritional protein. The 20% seed oil content (SOC) of soybean is much lower than that in most oil crops and the fatty acid composition of its native oil cannot meet the specifications for some applications in the food and industrial sectors. Considerable effort has been expended on soybean bioengineering to tailor fatty acid profiles and improve SOC.
A single 2′-O-methylation of ribosomal RNA gates assembly of a functional ribosome - Nature Structural & Molecular Biology
Abstract RNA modifications are widespread in biology and abundant in ribosomal RNA. However, the importance of these modifications is not well understood. We show that methylation of a single nucleotide, in the catalytic center of the large subunit, gates ribosome assembly. Massively parallel mutational scanning of the essential nuclear GTPase Nog2 identified important interactions with rRNA, particularly with the 2′-O-methylated A-site base Gm2922.
Instructional review of key factors to achieve successful outcomes when using low-intensity pulsed ultrasound in fracture repair
Abstract Low-intensity pulsed ultrasound (LIPUS) treatment of fractures has been available to the orthopaedic community for nearly three decades; however, it is still considered an experimental treatment by some clinicians, even though there is a wealth of clinical data. Based on the evaluation of clinical trial data, we have established key criteria which can lead to LIPUS success and avoid failure.
Distinguishing relapse from antidepressant withdrawal: clinical practice and antidepressant discontinuation studies
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Temperature dependence of diffusiophoresis via a novel microfluidic approach
Temperature dependence of diffusiophoresis via a novel microfluidic approach The temperature dependence of the diffusiophoretic mobility (DDP) is investigated experimentally and compared with theoretical predictions. These systematic measurements were made possible by a new microfluidic approach that enables truly steady state gradients to be imposed, and direct and repeatable measurements of diffusiophoretic migration over hours-long time scales.
Microscale hydrodynamic confinements: shaping liquids across length scales as a toolbox in life sciences
Microscale hydrodynamic confinements: shaping liquids across length scales as a toolbox in life sciences† David P. Taylor, ‡§ab Prerit Mathur, §ac Philippe Renaudb and Govind V. Kaigala *a Abstract Hydrodynamic phenomena can be leveraged to confine a range of biological and chemical species without needing physical walls.
David Taylor, Author at Victor Mochere
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Guide to buying energy efficient windows
The energy efficiency of building materials is becoming increasingly important. Check out the guide to buying energy efficient windows.
Full article: Centrally-acting anticholinergic drugs- associations with mortality, hospitalisation and cognitive decline following dementia diagnosis in people receiving antidepressant and antipsychotic drugs
Discussion Because it is unclear whether previously reported poor outcomes associated with anticholinergic drugs were due to the drugs themselves or to the illnesses they were treating (Andrade, 2019; Coupland et al., 2019), we sought to compare outcomes solely amongst patients receiving these classes of drugs in order to reduce confounding by indication.
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Rebecca H. Bind, Andrew J. Lawrence, Carolina Estevao, Katie Hazelgrove, Kristi Priestley, Lavinia Rebecchini, Riddhi Laijawala, Celeste Miller, Andy Healey, Joan Agwuna, Nick Sevdalis, Ioannis Bakolis, Rachel Davis, Maria Baldellou Lopez, Anthony J. Woods, Nikki Crane, Manonmani Manoharan, Alexandra Burton, Hannah Dye, Tim Osborn, Lorna Greenwood, Rosie Perkins, Paola Dazzan, Daisy Fancourt, Carmine M.
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Freya Diederich, Ebenezer Oloyede, David Taylor, Christian J. Bachmann Journal: The British Journal of Psychiatry , FirstView Published online by Cambridge University Press: 13 November 2025, pp. 1-8 View abstract Background Clozapine is licensed for treatment-resistant schizophrenia (TRS). Because of the risk of clozapine-induced agranulocytosis, its use requires regular haematological monitoring.
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Freya Diederich, Ebenezer Oloyede, David Taylor, Christian J. Bachmann Journal: The British Journal of Psychiatry , FirstView Published online by Cambridge University Press: 13 November 2025, pp. 1-8 View abstract Background Clozapine is licensed for treatment-resistant schizophrenia (TRS). Because of the risk of clozapine-induced agranulocytosis, its use requires regular haematological monitoring.
Investigating Diet as the Source of Tetrodotoxin in Pleurobranchaea maculata
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