Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
236
result(s) for
"Carr, Adrian"
Sort by:
Prodigy protein: Python package for zero-shot protein engineering using protein language models
Background
Protein Language Models (PLMs) are emerging as powerful tools for designing human proteins, including antibodies. These models can predict the effects of mutations in a zero-shot setting—without requiring additional fine-tuning—and suggest plausible amino acid substitutions.
Results
We introduce Protein Diversification and Generation through Yielded Mutations (Prodigy) Protein which provides several DirectedEvolution classes that introduce amino acid substitutions in a stepwise manner. Each substitution is evaluated using one of two scoring strategies, and the most promising candidates are sampled accordingly. Users can customize the number of evolution steps, specify target regions within the protein sequence, and set score thresholds to filter out low-quality substitutions during the design process.
Conclusion
Protein Diversification and Generation through Yielded Mutations (Prodigy) Protein is a fast and flexible tool for
in silico
protein design. It introduces a consistent and efficient probabilistic framework that leverages any masked language modeling Protein Language Model (PLM) available via Hugging Face. Unlike existing tools, Prodigy Protein can integrate multiple PLMs to design protein variants—an approach not currently supported by other publicly available software.
Journal Article
Integrating microRNA and mRNA expression profiling in Symbiodinium microadriaticum, a dinoflagellate symbiont of reef-building corals
Background
Animal and plant genomes produce numerous small RNAs (smRNAs) that regulate gene expression post-transcriptionally affecting metabolism, development, and epigenetic inheritance. In order to characterize the repertoire of endogenous smRNAs and potential gene targets in dinoflagellates, we conducted smRNA and mRNA expression profiling over 9 experimental treatments of cultures from
Symbiodinium microadriaticum
, a photosynthetic symbiont of scleractinian corals.
Results
We identified a set of 21 novel smRNAs that share stringent key features with functional microRNAs from other model organisms. smRNAs were predicted independently over all 9 treatments and their putative gene targets were identified. We found 1,720 animal-like target sites in the 3'UTRs of 12,858 mRNAs and 19 plant-like target sites in 51,917 genes. We assembled a transcriptome of 58,649 genes and determined differentially expressed genes (DEGs) between treatments. Heat stress was found to produce a much larger number of DEGs than other treatments that yielded only few DEGs. Analysis of DEGs also revealed that minicircle-encoded photosynthesis proteins seem to be common targets of transcriptional regulation. Furthermore, we identified the core RNAi protein machinery in
Symbiodinium
.
Conclusions
Integration of smRNA and mRNA expression profiling identified a variety of processes that could be under microRNA control, e.g. protein modification, signaling, gene expression, and response to DNA damage. Given that
Symbiodinium
seems to have a paucity of transcription factors and differentially expressed genes, identification and characterization of its smRNA repertoire establishes the possibility of a range of gene regulatory mechanisms in dinoflagellates acting post-transcriptionally.
Journal Article
Biochemical Diversification through Foreign Gene Expression in Bdelloid Rotifers
Bdelloid rotifers are microinvertebrates with unique characteristics: they have survived tens of millions of years without sexual reproduction; they withstand extreme desiccation by undergoing anhydrobiosis; and they tolerate very high levels of ionizing radiation. Recent evidence suggests that subtelomeric regions of the bdelloid genome contain sequences originating from other organisms by horizontal gene transfer (HGT), of which some are known to be transcribed. However, the extent to which foreign gene expression plays a role in bdelloid physiology is unknown. We address this in the first large scale analysis of the transcriptome of the bdelloid Adineta ricciae: cDNA libraries from hydrated and desiccated bdelloids were subjected to massively parallel sequencing and assembled transcripts compared against the UniProtKB database by blastx to identify their putative products. Of ~29,000 matched transcripts, ~10% were inferred from blastx matches to be horizontally acquired, mainly from eubacteria but also from fungi, protists, and algae. After allowing for possible sources of error, the rate of HGT is at least 8%-9%, a level significantly higher than other invertebrates. We verified their foreign nature by phylogenetic analysis and by demonstrating linkage of foreign genes with metazoan genes in the bdelloid genome. Approximately 80% of horizontally acquired genes expressed in bdelloids code for enzymes, and these represent 39% of enzymes in identified pathways. Many enzymes encoded by foreign genes enhance biochemistry in bdelloids compared to other metazoans, for example, by potentiating toxin degradation or generation of antioxidants and key metabolites. They also supplement, and occasionally potentially replace, existing metazoan functions. Bdelloid rotifers therefore express horizontally acquired genes on a scale unprecedented in animals, and foreign genes make a profound contribution to their metabolism. This represents a potential mechanism for ancient asexuals to adapt rapidly to changing environments and thereby persist over long evolutionary time periods in the absence of sex.
Journal Article
Genome-wide analysis clarifies the population genetic structure of wild gilthead sea bream (Sparus aurata)
Gilthead sea bream is an important target for both recreational and commercial fishing in Europe, where it is also one of the most important cultured fish. Its distribution ranges from the Mediterranean to the African and European coasts of the North-East Atlantic. Until now, the population genetic structure of this species in the wild has largely been studied using microsatellite DNA markers, with minimal genetic differentiation being detected. In this geographically widespread study, 958 wild gilthead sea bream from 23 locations within the Mediterranean Sea and Atlantic Ocean were genotyped at 1159 genome-wide SNP markers by RAD sequencing. Outlier analyses identified 18 loci potentially under selection. Neutral marker analyses identified weak subdivision into three genetic clusters: Atlantic, West, and East Mediterranean. The latter group could be further subdivided into an Ionian/Adriatic and an Aegean group using the outlier markers alone. Seascape analysis suggested that this differentiation was mainly due to difference in salinity, this being also supported by preliminary genomic functional analysis. These results are of fundamental importance for the development of proper management of this species in the wild and are a first step toward the study of the potential genetic impact of the sea bream aquaculture industry.
Journal Article
Insights into electrosensory organ development, physiology and evolution from a lateral line-enriched transcriptome
The anamniote lateral line system, comprising mechanosensory neuromasts and electrosensory ampullary organs, is a useful model for investigating the developmental and evolutionary diversification of different organs and cell types. Zebrafish neuromast development is increasingly well understood, but neither zebrafish nor Xenopus is electroreceptive and our molecular understanding of ampullary organ development is rudimentary. We have used RNA-seq to generate a lateral line-enriched gene-set from late-larval paddlefish (Polyodon spathula). Validation of a subset reveals expression in developing ampullary organs of transcription factor genes critical for hair cell development, and genes essential for glutamate release at hair cell ribbon synapses, suggesting close developmental, physiological and evolutionary links between non-teleost electroreceptors and hair cells. We identify an ampullary organ-specific proneural transcription factor, and candidates for the voltage-sensing L-type Cav channel and rectifying Kv channel predicted from skate (cartilaginous fish) ampullary organ electrophysiology. Overall, our results illuminate ampullary organ development, physiology and evolution.
Journal Article
Identification of MicroRNAs in the Coral Stylophora pistillata
Coral reefs are major contributors to marine biodiversity. However, they are in rapid decline due to global environmental changes such as rising sea surface temperatures, ocean acidification, and pollution. Genomic and transcriptomic analyses have broadened our understanding of coral biology, but a study of the microRNA (miRNA) repertoire of corals is missing. miRNAs constitute a class of small non-coding RNAs of ∼22 nt in size that play crucial roles in development, metabolism, and stress response in plants and animals alike. In this study, we examined the coral Stylophora pistillata for the presence of miRNAs and the corresponding core protein machinery required for their processing and function. Based on small RNA sequencing, we present evidence for 31 bona fide microRNAs, 5 of which (miR-100, miR-2022, miR-2023, miR-2030, and miR-2036) are conserved in other metazoans. Homologues of Argonaute, Piwi, Dicer, Drosha, Pasha, and HEN1 were identified in the transcriptome of S. pistillata based on strong sequence conservation with known RNAi proteins, with additional support derived from phylogenetic trees. Examination of putative miRNA gene targets indicates potential roles in development, metabolism, immunity, and biomineralisation for several of the microRNAs. Here, we present first evidence of a functional RNAi machinery and five conserved miRNAs in S. pistillata, implying that miRNAs play a role in organismal biology of scleractinian corals. Analysis of predicted miRNA target genes in S. pistillata suggests potential roles of miRNAs in symbiosis and coral calcification. Given the importance of miRNAs in regulating gene expression in other metazoans, further expression analyses of small non-coding RNAs in transcriptional studies of corals should be informative about miRNA-affected processes and pathways.
Journal Article
Investigating Genetic Diversity and Genomic Signatures of Hatchery-Induced Evolution in Gilthead Seabream (Sparus aurata) Populations
The identification of the genetic basis of domestication in fish species is of timely importance for the aquaculture industry in order to increase productivity, quality, and the welfare of farmed fish. The goal of this study is to investigate the largely unknown aquaculture-induced evolution in gilthead seabream, which is one of the most important farmed fish in the Mediterranean region. We used a panel of 1159 genome-wide SNPs, and genotyped 956 fish from 23 wild populations of Mediterranean-wide distribution and 362 farmed fish from five Greek hatcheries. We assessed the genetic diversity of the sampled populations and contrasted the results of four different approaches of outlier detection methods. We recognized one very strong candidate and two good candidate SNPs with evidence for aquaculture-induced evolution in gilthead seabream. The annotation of these SNPs revealed neighboring genes with biological roles from stress tolerance and disease resistance to sexual maturation that may explain our observations. In conclusion, we demonstrate that the genome of gilthead seabream, despite the fact that the species is often suggested to be in the early stages of the domestication process, shows evidence of aquaculture-induced evolution. We report on a list of genes that may explain our observations and that may be investigated further. We anticipate that our findings will stimulate additional research with the use of SNP panels of higher density that can elucidate the genomic architecture of domestication in this species of high aquacultural interest.
Journal Article
Space and time in organizational change management
Purpose - The paper aims to introduce the manner in which management and organization theory have viewed space and time as significant resources and to put forward a number of more contemporary views as to how space and time is both managed and experienced.Design methodology approach - The paper adopts a postmodern approach in assembling what it regards as \"fragments\" from a variety of disciplinary discourses on space and time. Each fragment presents, putatively, a different voice, theme or motif which are intended to help the reader better understand the trajectories contained in the other papers in the volume.Findings - The paper finds that conceptions of space and time are fundamental to the manner in which organizations are managed and organized and are a symbolic order inter-related to themes of power and control. The manner in which we experience space and time is open to manipulation and specifically a form compression that displaces critical reflection and may make individuals prone to external locus of control. The manner in which time and space are linked to the suppression of human agency and the imperatives of capitalism cannot be overestimated and require reflexive consideration.Originality value - The paper, and the volume as a whole, recognises time and space as social constructions and thus open to \"reconstruction\". Space and time are not simple a priori categories that are fixed, immutable absolutes and knowable entities. The recognition of the intersubjective \"nature\" of space and time is shown to help us better appreciate the different manner in which space and time is experienced and the manner in which space and time are used in the management of change.
Journal Article
Space and time and organization change
The papers in this e-book originate from the 4th International Critical Management Studies Conference held at Cambridge University in July 2005. The articles look at the way in which management and organization theory has viewed space and time as significant resources and they put forward a number of more contemporary views as to how space and time is both managed and experienced. The papers recognize time and space as social constructions and thus open to 'reconstruction'. Space and time are not simple a priori categories that are fixed, immutable absolutes and knowable entities. The recogni
Book