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Journal articleHailu E, Cantillon D, Madrazo C, et al., 2023,
Lack of methoxy- mycolates characterizes the geographically restricted lineage 7 of<i> Mycobacterium</i><i> tuberculosis</i> complex
, MICROBIAL GENOMICS, Vol: 9, ISSN: 2057-5858 -
Journal articleOsborne OG, Dobreva MP, Papadopulos AST, et al., 2023,
Mapping the root systems of individual trees in a natural community using genotyping-by-sequencing
, New Phytologist, Vol: 238, Pages: 1305-1317, ISSN: 0028-646X•The architecture of root systems is an important driver of plant fitness, competition and ecosystem processes. However, the methodological difficulty of mapping roots hampers the study of these processes. Existing approaches to match individual plants to belowground samples are low throughput and species specific. Here, we developed a scalable sequencing-based method to map the root systems of individual trees across multiple species. We successfully applied it to a tropical dry forest community in the Brazilian Caatinga containing 14 species. • We sequenced all 42 individual shrubs and trees in a 14 × 14 m plot using double-digest restriction site-associated sequencing (ddRADseq). We identified species-specific markers and individual-specific haplotypes from the data. We matched these markers to the ddRADseq data from 100 mixed root samples from across the centre (10 × 10 m) of the plot at four different depths using a newly developed R package. • We identified individual root samples for all species and all but one individual. There was a strong significant correlation between belowground and aboveground size measurements, and we also detected significant species-level root-depth preference for two species. • The method is more scalable and less labour intensive than the current techniques and is broadly applicable to ecology, forestry and agricultural biology.
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PatentKourelis J, Marchal C, Kamoun S, 2023,
MODIFYING THE IMMUNE RESPONSE IN PLANTS
, EP4170039A1Chimeric proteins comprising a binding molecule, preferably a single chain antibody, linked to a plant immune receptor protein, are disclosed.
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Journal articleHuang Z, Lai PF, Cocker ATH, et al., 2023,
Roles of N-linked glycosylation and glycan-binding proteins in placentation: trophoblast infiltration, immunomodulation, angiogenesis, and pathophysiology
, Biochemical Society Transactions, Vol: 51, Pages: 639-653, ISSN: 0300-5127Protein N-linked glycosylation is a structurally diverse post-translational modification that stores biological information in a larger order of magnitude than other post-translational modifications such as phosphorylation, ubiquitination and acetylation. This gives N-glycosylated proteins a diverse range of properties and allows glyco-codes (glycan-related information) to be deciphered by glycan-binding proteins (GBPs). The intervillous space of the placenta is richly populated with membrane-bound and secreted glycoproteins. Evidence exists to suggest that altering the structural nature of their N-glycans can impact several trophoblast functions, which include those related to interactions with decidual cells. This review summarizes trophoblast-related activities influenced by N-glycan-GBP recognition, exploring how different subtypes of trophoblasts actively adapt to characteristics of the decidualized endometrium through cell-specific expression of N-glycosylated proteins, and how these cells receive decidua-derived signals via N-glycan-GBP interactions. We highlight work on how changes in N-glycosylation relates to the success of trophoblast infiltration, interactions of immunomodulators, and uterine angiogenesis. We also discuss studies that suggest aberrant N-glycosylation of trophoblasts may contribute to the pathogenesis of pregnancy complications (e.g. pre-eclampsia, early spontaneous miscarriages and hydatidiform mole). We propose that a more in-depth understanding of how N-glycosylation shapes trophoblast phenotype during early pregnancy has the potential to improve our approach to predicting, diagnosing and alleviating poor maternal/fetal outcomes associated with placental dysfunction.
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Journal articleCornford R, Spooner F, McRae L, et al., 2023,
Ongoing over-exploitation and delayed responses to environmental change highlight the urgency for action to promote vertebrate recoveries by 2030
, PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, Vol: 290, ISSN: 0962-8452 -
Journal articleLow WW, Seddon C, Beis K, et al., 2023,
The Interaction of the F-Like Plasmid-Encoded TraN Isoforms with Their Cognate Outer Membrane Receptors
, JOURNAL OF BACTERIOLOGY, Vol: 205, ISSN: 0021-9193- Author Web Link
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- Citations: 1
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Journal articleChen T, Hojka M, Davey P, et al., 2023,
Engineering α-carboxysomes into chloroplasts to support autotrophic photosynthesis
, Nature Communications, ISSN: 2041-1723 -
Journal articleShen Y, Cai W, Prentice IC, et al., 2023,
Community abundance of resprouting in woody plants reflects fire return time, intensity, and type
, Forests, Vol: 14, Pages: 1-13, ISSN: 1999-4907Plants in fire-prone ecosystems have evolved a variety of mechanisms to resist or adapt to fire. Post-fire resprouting is a key adaptation that promotes rapid ecosystem recovery and hence has a major impact on the terrestrial carbon cycle. However, our understanding of how the incidence of resprouting varies in different fire regimes is largely qualitative. The increasing availability of plant trait data and plot-based species cover data provides an opportunity to quantify the relationships between fire-related traits and fire properties. We investigated the quantitative relationship between fire frequency (expressed as the fire return time) and the proportion of resprouters in woody plants using plot data on species cover from Australia and Europe. We also examined the relationship between the proportion of resprouters and gross primary production (GPP) and grass cover, where GPP was assumed to reflect fuel loads and hence fire intensity, while grass cover was considered to be an indicator of the likelihood of ground fire and the speed of fire spread, using generalised linear modelling. The proportion of resprouting species decreased significantly as the fire return time increased. When the fire return time was considered along with other aspects of the fire regime, the proportion of resprouters had significant negative relationships with the fire return time and grass cover and a significant positive relationship with GPP. These findings demonstrate that plants with the ability to resprout occur more often where fire regimes are characterised by high-frequency and high-intensity crown fires. Establishing quantitative relationships between the incidence of resprouting and the fire return time and fire type provides a basis for modelling resprouting as a consequence of the characteristics of the fire regime, which in turn makes it possible to model the consequences of changing fire regimes on ecosystem properties.
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Journal articlevan Thor JJ, Champion PM, 2023,
Photoacid dynamics in the green fluorescent protein
, Annual Review of Physical Chemistry, Vol: 74, Pages: 1-22, ISSN: 0066-426XThe photoacid dynamics of fluorescent proteins include both electronic excited- and ground-state mechanisms of proton transfer. The associated characteristic timescales of these reactions range over many orders of magnitude, and the tunneling, barrier crossing, and relevant thermodynamics have in certain cases been linked to coherent nuclear motion. We review the literature and summarize the experiments and theory that demonstrate proton tunneling in the electronic ground state of the green fluorescent protein (GFP). We also discuss the excited-state proton-transfer reaction of GFP that takes place on the picosecond timescale. Although this reaction has been investigated using several vibrational spectroscopic methods, the interpretation remains unsettled. We discuss recent advances as well as remaining questions, in particular those related to the vibrational mode couplings that involve low-frequency modulations of chromophore vibrations on the timescale of proton transfer.
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Journal articleGhani L, Zhang X, Munk CF, et al., 2023,
Tris(hydroxymethyl)aminomethane linker-bearing triazine-based triglucosides for solubilization and stabilization of membrane proteins
, Bioconjugate Chemistry, Vol: 34, Pages: 739-747, ISSN: 1043-1802High-resolution membrane protein structures are essential for a fundamental understanding of the molecular basis of diverse cellular processes and for drug discovery. Detergents are widely used to extract membrane-spanning proteins from membranes and maintain them in a functional state for downstream characterization. Due to limited long-term stability of membrane proteins encapsulated in conventional detergents, development of novel agents is required to facilitate membrane protein structural study. In the current study, we designed and synthesized tris(hydroxymethyl)aminomethane linker-bearing triazine-based triglucosides (TTGs) for solubilization and stabilization of membrane proteins. When these glucoside detergents were evaluated for four membrane proteins including two G protein-coupled receptors, a few TTGs including TTG-C10 and TTG-C11 displayed markedly enhanced behaviors toward membrane protein stability relative to two maltoside detergents [DDM (n-dodecyl-β-d-maltoside) and LMNG (lauryl maltose neopentyl glycol)]. This is a notable feature of the TTGs as glucoside detergents tend to be inferior to maltoside detergents at stabilizing membrane proteins. The favorable behavior of the TTGs for membrane protein stability is likely due to the high hydrophobicity of the lipophilic groups, an optimal range of hydrophilic–lipophilic balance, and the absence of cis–trans isomerism.
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Journal articleLarrouy-Maumus G, 2023,
A whole cell-based Matrix-assisted laser desorption/ionization mass spectrometry lipidomic assay for the discovery of compounds that target lipid a modifications
, Frontiers in Microbiology, Vol: 14, Pages: 1-7, ISSN: 1664-302XIntroduction: Matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) is a powerful analytical technique that has been applied to a wide variety of applications ranging from proteomics to clinical diagnostics. One such application is its use as a tool for discovery assays, such as monitoring the inhibition of purified proteins. With the global threat from antimicrobial-resistant (AMR) bacteria, new and innovative solutions are required to identify new molecules that could revert bacterial resistance and/or target virulence factors. Here, we used a whole cell-based MALDI-TOF lipidomic assay using a routine MALDI Biotyper Sirius system operating in linear negative ion mode combined with the MBT Lipid Xtract kit to discover molecules targeting bacteria that are resistant to polymyxins, which are considered last-resort antibiotics.Methods: A library of 1200 natural compounds was tested against an E. coli strain expressing mcr-1, which is known to modify lipid A by adding phosphoethanolamine (pETN), making the strain resistant to colistin.Results and Discussion: Using this approach, we identified 8 compounds that led to a decrease in this lipid A modification by MCR-1 and could potentially be employed to revert resistance. Taken together, as-proof-of-principle, the data we report here represent a new workflow based on the analysis of bacterial lipid A by routine MALDI-TOF for the discovery of inhibitors that could target bacterial viability and/or virulence.
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Journal articleMielcarek M, Isalan M, 2023,
A minimal region of the HSP90AB1 promoter is suitable for ubiquitous expression in different somatic tissues with applicability for gene therapy
, Frontiers in Molecular Biosciences, Vol: 10, ISSN: 2296-889XHuntington’s disease (HD) is a multi-tissue failure disorder for which there is no cure. We have previously shown an effective therapeutic approach limited mainly to the central nervous system, based on a synthetic zinc finger (ZF) transcription repressor gene therapy, but it would be important to target other tissues as well. In this study, we identify a novel minimal HSP90AB1 promoter region that can efficiently control expression not only in the CNS but also in other affected HD tissues. This promoter-enhancer is effective in driving expression of ZF therapeutic molecules in both HD skeletal muscles and the heart, in the symptomatic R6/1 mouse model. Moreover, for the first time we show that ZF molecules repressing mutant HTT reverse transcriptional pathological remodelling in HD hearts. We conclude that this HSP90AB1 minimal promoter may be used to target multiple HD organs with therapeutic genes. The new promoter has the potential to be added to the portfolio of gene therapy promoters, for use where ubiquitous expression is needed.
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Journal articleLiu D, Semenchuk P, Essl F, et al., 2023,
The impact of land use on non-native species incidence and number in local assemblages worldwide
, NATURE COMMUNICATIONS, Vol: 14- Author Web Link
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- Citations: 5
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Journal articleSantini L, Tobias JA, Callaghan C, et al., 2023,
Global patterns and predictors of avian population density
, GLOBAL ECOLOGY AND BIOGEOGRAPHY, ISSN: 1466-822X -
Journal articleWyer C, Brian H, Cator L, 2023,
Release from sexual selection leads to rapid genome-wide evolution in Aedes aegypti
, Current Biology, Vol: 33, Pages: 1351-1357.e5, ISSN: 0960-9822The yellow fever mosquito, Aedes aegypti, mates in flight as part of ephemeral aggregations termed swarms. Swarms contain many more males than females, and males are thought to be subject to intense sexual selection.1,2 However, which male traits are involved in mating success and the genetic basis of these traits remains unclear. We used an experimental evolution approach to measure genome-wide responses of Ae. aegypti evolved in the presence and absence of sexual selection. These data revealed for the first time how sexual selection shapes the genome of this important species. We found that populations evolved under sexual selection retained greater genetic similarity to the ancestral population and a higher effective population size than populations evolving without sexual selection. When we compared evolutionary regimes, we found that genes associated with chemosensation responded rapidly to the elimination of sexual selection. Knockdown of one high-confidence candidate gene identified in our analysis significantly decreased male insemination success, further suggesting that genes related to male sensory perception are under sexual selection. Several mosquito control technologies involve the release of males from captive populations into the wild. For these interventions to work, a released male must compete against wild males to successfully inseminate a female. Our results suggest that maintaining the intensity of sexual selection in captive populations used in mass-releases is important for sustaining both male competitive ability and overall genetic similarity to field populations.
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Journal articleWong JLC, Romano M, Kerry LE, et al., 2023,
Author Correction: OmpK36-mediated Carbapenem resistance attenuates ST258 Klebsiella pneumoniae in vivo.
, Nat Commun, Vol: 14 -
Journal articleStegemann A, Liu S, Retana Romero OA, et al., 2023,
Prefrontal engrams of long-term fear memory perpetuate pain perception
, NATURE NEUROSCIENCE, ISSN: 1097-6256- Author Web Link
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- Citations: 3
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Journal articleLiu M, Shen Y, Gonzalez-Samperiz P, et al., 2023,
Holocene climates of the Iberian Penisula: pollen-based reconstructions of changes in the west-east gradient of temperature and moisture
, Climate of the Past, Vol: 19, Pages: 803-834, ISSN: 1814-9324The Iberian Peninsula is characterised by a steep west-east moisture gradient today, reflecting the dominance of maritime influences along the Atlantic coast and more Mediterranean-type climate further east. Holocene pollen records from the Peninsula suggest that this gradient was less steep during the mid-Holocene, possibly reflecting the impact of orbital changes on circulation and thus regional patterns in climate. Here we use 7214 pollen samples from 117 sites covering part or all of the last 12,000 years to reconstruct changes in seasonal temperature and in moisture across the Iberian Peninsula quantitatively. We show that there is an increasing trend in winter temperature at a regional scale, consistent with known changes in winter insolation. However, summer temperatures do not show the decreasing trend through the Holocene that would be expected if they were a direct response to insolation forcing. We show that summer temperature is strongly correlated with plant-available moisture (α), as measured by the ratio of actual evapotranspiration to equilibrium evapotranspiration, which declines through the Holocene. The reconstructions also confirm that the west-east gradient in moisture was considerably less steep than today during the mid-Holocene, indicating that atmospheric circulation changes (possibly driven by orbital changes) have been important determinants of the Holocene climate of the region.
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Journal articlePatkowski J, Dahlberg T, Amin H, et al., 2023,
The F-pilus biomechanical adaptability accelerates conjugative dissemination of antimicrobial resistance and biofilm formation
, Nature Communications, Vol: 14, Pages: 1-14, ISSN: 2041-1723Conjugation is used by bacteria to propagate antimicrobial resistance (AMR) in the environment. Central to this process are widespread conjugative F-pili that establish the connection between donor and recipient cells, thereby facilitating the spread of IncF plasmids among enteropathogenic bacteria. Here, we show that the F-pilus is highly flexible but robust at the same time, properties that increase its resistance to thermochemical and mechanical stresses. By a combination of biophysical and molecular dynamics methods, we establish that the presence of phosphatidylglycerol molecules in the F-pilus contributes to the structural stability of the polymer. Moreover, this structural stability is important for successful delivery of DNA during conjugation and facilitates rapid formation of biofilms in harsh environmental conditions. Thus, our work highlights the importance of F-pilus structural adaptations for the efficient spread of AMR genes in a bacterial population and for the formation of biofilms that protect against the action of antibiotics.
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Journal articleVadas O, Pacheco NDS, Chao K, et al., 2023,
Structural and regulatory insights into the glideosome- associated connector from Toxoplasma gondii
, eLife, Vol: 12, ISSN: 2050-084XThe phylum of Apicomplexa groups intracellular parasites that employ substrate-dependent gliding motility to invade host cells, egress from the infected cells, and cross biological barriers. The glideosome-associated connector (GAC) is a conserved protein essential to this process. GAC facilitates the association of actin filaments with surface transmembrane adhesins and the efficient transmission of the force generated by myosin translocation of actin to the cell surface substrate. Here, we present the crystal structure of Toxoplasma gondii GAC and reveal a unique, supercoiled armadillo repeat region that adopts a closed ring conformation. Characterisation of the solution properties together with membrane and F-actin binding interfaces suggests that GAC adopts several conformations from closed to open and extended. A multi-conformational model for assembly and regulation of GAC within the glideosome is proposed.
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OtherWalwyn-Brown K, Pugh J, Cocker ATH, et al., 2023,
Supplementary Figure from Phosphoantigen-Stimulated γδ T Cells Suppress Natural Killer–Cell Responses to Missing-Self
<jats:p>Supplementary Figure from Phosphoantigen-Stimulated γδ T Cells Suppress Natural Killer–Cell Responses to Missing-Self</jats:p>
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OtherWalwyn-Brown K, Pugh J, Cocker ATH, et al., 2023,
Data from Phosphoantigen-Stimulated γδ T Cells Suppress Natural Killer–Cell Responses to Missing-Self
<jats:p><div>Abstract<p>γδ T cells stimulated by phosphoantigens (pAg) are potent effectors that secrete Th1 cytokines and kill tumor cells. Consequently, they are considered candidates for use in cancer immunotherapy. However, they have proven only moderately effective in several clinical trials. We studied the consequences of pAg-stimulated γδ T-cell interactions with natural killer (NK) cells and CD8<sup>+</sup> T cells, major innate and adaptive effectors, respectively. We found that pAg-stimulated γδ T cells suppressed NK-cell responses to “missing-self” but had no effect on antigen-specific CD8<sup>+</sup> T-cell responses. Extensive analysis of the secreted cytokines showed that pAg-stimulated γδ T cells had a proinflammatory profile. CMV-pp65–specific CD8<sup>+</sup> T cells primed with pAg-stimulated γδ T cells showed little effect on responses to pp65-loaded target cells. By contrast, NK cells primed similarly with γδ T cells had impaired capacity to degranulate and produce IFNγ in response to HLA class I–deficient targets. This effect depended on BTN3A1 and required direct contact between NK cells and γδ T cells. γδ T-cell priming of NK cells also led to a downregulation of NKG2D and NKp44 on NK cells. Every NK-cell subset was affected by γδ T cell–mediated immunosuppression, but the strongest effect was on KIR<sup>+</sup>NKG2A<sup>–</sup> NK cells. We therefore report a previously unknown function for γδ T cells, as brakes of NK-cell responses to “missing-self.” This provides a new perspective for optimizing the use of γδ T cells in cancer immunotherapy and for assessing their role in immune responses
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OtherWalwyn-Brown K, Pugh J, Cocker ATH, et al., 2023,
Supplementary Figure from Phosphoantigen-Stimulated γδ T Cells Suppress Natural Killer–Cell Responses to Missing-Self
<jats:p>Supplementary Figure from Phosphoantigen-Stimulated γδ T Cells Suppress Natural Killer–Cell Responses to Missing-Self</jats:p>
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OtherWalwyn-Brown K, Pugh J, Cocker ATH, et al., 2023,
Data from Phosphoantigen-Stimulated γδ T Cells Suppress Natural Killer–Cell Responses to Missing-Self
<jats:p><div>Abstract<p>γδ T cells stimulated by phosphoantigens (pAg) are potent effectors that secrete Th1 cytokines and kill tumor cells. Consequently, they are considered candidates for use in cancer immunotherapy. However, they have proven only moderately effective in several clinical trials. We studied the consequences of pAg-stimulated γδ T-cell interactions with natural killer (NK) cells and CD8<sup>+</sup> T cells, major innate and adaptive effectors, respectively. We found that pAg-stimulated γδ T cells suppressed NK-cell responses to “missing-self” but had no effect on antigen-specific CD8<sup>+</sup> T-cell responses. Extensive analysis of the secreted cytokines showed that pAg-stimulated γδ T cells had a proinflammatory profile. CMV-pp65–specific CD8<sup>+</sup> T cells primed with pAg-stimulated γδ T cells showed little effect on responses to pp65-loaded target cells. By contrast, NK cells primed similarly with γδ T cells had impaired capacity to degranulate and produce IFNγ in response to HLA class I–deficient targets. This effect depended on BTN3A1 and required direct contact between NK cells and γδ T cells. γδ T-cell priming of NK cells also led to a downregulation of NKG2D and NKp44 on NK cells. Every NK-cell subset was affected by γδ T cell–mediated immunosuppression, but the strongest effect was on KIR<sup>+</sup>NKG2A<sup>–</sup> NK cells. We therefore report a previously unknown function for γδ T cells, as brakes of NK-cell responses to “missing-self.” This provides a new perspective for optimizing the use of γδ T cells in cancer immunotherapy and for assessing their role in immune responses
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Journal articleCherta-Murillo A, Danckert NP, Valdivia-Garcia M, et al., 2023,
Gut microbiota fermentation profiles of pre-digested mycoprotein (Quorn) using faecal batch cultures <i>in vitro</i>: a preliminary study
, INTERNATIONAL JOURNAL OF FOOD SCIENCES AND NUTRITION, Vol: 74, Pages: 327-337, ISSN: 0963-7486 -
Journal articleGkourtsouli-Antoniadou I, Ewing SRR, Hudson G, et al., 2023,
Age-specific survival in an English Twite <i>Linaria flavirostris</i> population
, BIRD STUDY, Vol: 70, Pages: 59-63, ISSN: 0006-3657 -
Journal articleGroner VP, Williams JJ, Pearson RG, 2023,
Limited evidence for quantitative contribution of rare and endangered species to agricultural production
, AGRICULTURE ECOSYSTEMS & ENVIRONMENT, Vol: 345, ISSN: 0167-8809- Author Web Link
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- Citations: 1
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Journal articleGe X, Peng L, Vogler AP, et al., 2023,
Massive gene rearrangements of mitochondrial genomes and implications for the phylogeny of Trichoptera (Insecta)
, SYSTEMATIC ENTOMOLOGY, Vol: 48, Pages: 278-295, ISSN: 0307-6970- Author Web Link
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- Citations: 4
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Journal articleAughey G, Grimes K, Forsberg E, et al., 2023,
NuRD independent Mi-2 activity represses ectopic gene expression during neuronal maturation
, EMBO Reports, Vol: 24, Pages: 1-15, ISSN: 1469-221XDuring neuronal development, extensive changes to chromatin states occur to regulate lineage-specific gene expression. The molecular factors underlying the repression of non-neuronal genes in differentiated neurons are poorly characterised. The Mi2/NuRD complex is a multiprotein complex with nucleosome remodelling and histone deacetylase activity. Whilst NuRD has previously been implicated in the development of nervous system tissues, the precise nature of the gene expression programmes that it coordinates is ill-defined. Furthermore, evidence from several species suggests that Mi-2 may be incorporated into multiple complexes that may not possess histone deacetylase activity. We show that Mi-2 activity is required for suppressing ectopic expression of germline genes in neurons independently of HDAC1/NuRD, whilst components of NuRD, including Mi-2, regulate neural gene expression to ensure proper development of the larval nervous system. We find that Mi-2 binding in the genome is dynamic during neuronal maturation, and Mi-2-mediated repression of ectopic gene expression is restricted to the early stages of neuronal development, indicating that Mi-2/NuRD is required for establishing stable neuronal transcriptomes during the early stages of neuronal differentiation.
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Journal articleLedesma Amaro R, Selles Vidal L, Isalan M, et al., 2023,
A primer to directed evolution: current methodologies and future directions
, RSC Chemical Biology, Vol: 4, Pages: 271-291, ISSN: 2633-0679Directed evolution is one of the most powerful tools for protein engineering and functions by harnessing natural evolution, but on a shorter timescale. It enables the rapid selection of variants of biomolecules with properties that make them more suitable for specific applications. Since the first in vitro evolution experiments performed by Sol Spiegelman in 1967, a wide range of techniques have been developed to tackle the main two steps of directed evolution: genetic diversification (library generation), and isolation of the variants of interest. This review covers the main modern methodologies, discussing the advantages and drawbacks of each, and hence the considerations for designing directed evolution experiments. Furthermore, the most recent developments are discussed, showing how advances in the handling of ever larger library sizes are enabling new research questions to be tackled.
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