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A last-in first-out stack data structure implemented in DNA.

ABSTRACT: DNA-based memory systems are being reported with increasing frequency. However, dynamic DNA data structures able to store and recall information in an ordered way, and able to be interfaced with external nucleic acid computing circuits, have so far received little attention. Here we present an in vitro implementation of a stack data structure using DNA polymers. The stack is able to record combinations of two different DNA signals, release the signals into solution in reverse order, and then re-record. We explore the accuracy limits of the stack data structure through a stochastic rule-based model of the underlying polymerisation chemistry. We derive how the performance of the stack increases with the efficiency of washing steps between successive reaction stages, and report how stack performance depends on the history of stack operations under inefficient washing. Finally, we discuss refinements to improve molecular synchronisation and future open problems in implementing an autonomous chemical data structure.

SUBMITTER: Lopiccolo A

PROVIDER: S-EPMC8358042 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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A last-in first-out stack data structure implemented in DNA.

Lopiccolo Annunziata A Shirt-Ediss Ben B Torelli Emanuela E Olulana Abimbola Feyisara Adedeji AFA Castronovo Matteo M Fellermann Harold H Krasnogor Natalio N

Nature communications 20210811 1

DNA-based memory systems are being reported with increasing frequency. However, dynamic DNA data structures able to store and recall information in an ordered way, and able to be interfaced with external nucleic acid computing circuits, have so far received little attention. Here we present an in vitro implementation of a stack data structure using DNA polymers. The stack is able to record combinations of two different DNA signals, release the signals into solution in reverse order, and then re- ...[more]

PMID: 34381035

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Project description:The thymine-uracil exchange constitutes one of the major chemical differences between DNA and RNA. Although these two bases form the same Watson-Crick base pairs with adenine and are equivalent for both information storage and transmission, uracil incorporation in DNA is usually a mistake that needs to be excised. There are two ways for uracil to appear in DNA: thymine replacement and cytosine deamination. Most DNA polymerases readily incorporate dUMP as well as dTMP depending solely on the availability of the d(U/T)TP building block nucleotides. Cytosine deamination results in mutagenic U:G mismatches that must be excised. The repair system, however, also excises U from U:A "normal" pairs. It is therefore crucial to limit thymine-replacing uracils.dUTP is constantly produced in the pyrimidine biosynthesis network. To prevent uracil incorporation into DNA, representatives of the dUTP nucleotidohydrolase (dUTPase) enzyme family eliminate excess dUTP. This Account describes recent studies that have provided important detailed insights into the structure and function of these essential enzymes.dUTPases typically possess exquisite specificity and display an intriguing homotrimer active site architecture. Conserved residues from all three monomers contribute to each of the three active sites within the dUTPase. Although even dUTPases from evolutionarily distant species possess similar structural and functional traits, in a few cases, a monomer dUTPase mimics the trimer structure through an unusual folding pattern. Catalysis proceeds by way of an SN2 mechanism; a water molecule initiates in-line nucleophilic attack. The dUTPase binding pocket is highly specific for uracil. Phosphate chain coordination involves Mg2+ and is analogous to that of DNA polymerases. Because of conformational changes in the enzyme during catalysis, most crystal structures have not resolved the residues in the C-terminus. However, recent high-resolution structures are beginning to provide in-depth structural information about this region of the protein.The dUTPase family of enzymes also shows promise as novel targets for anticancer and antimicrobial therapies. dUTPase is upregulated in human tumor cells. In addition, dUTPase inhibitors could also fight infectious diseases such as malaria and tuberculosis. In these respective pathogens, Plasmodium falciparum and Mycobacterium tuberculosis, the biosynthesis of dTMP relies exclusively on dUTPase activity.

Project description:BackgroundBy means of job crafting (JC) employees shape and customize their job design to align it with their preferences. Research has so far shown that such bottom-up proactivity can be stimulated via JC interventions. While the overall effectiveness behind these interventions has been supported, it is unclear how to implement these interventions to make their effects lasting.MethodsThe overall aim of this project will be to investigate how to implement JC interventions with lasting effects. We will apply a group concept mapping (GCM) methodology, which is a mixed methods approach of exploratory nature for engaging stakeholder groups in a structured conceptualization process. As part of concept mapping procedures, brainstorming sessions will be conducted with experts in job crafting to identify factors expected to make job crafting intervention effects lasting. These factors will be sorted by similarity and rated by each participant in regard to their perceived importance and feasibility to ensure lasting, sustainable effects. The data will be analyzed using multidimensional scaling (MDS), hierarchical cluster analysis, and descriptive and inferential statistics, resulting in a visual representation of conceptually distinguished clusters representing the factors influencing the sustainability of JC interventions. In the final step, a workshop will be conducted with the participants to facilitate the interpretation of the results.Results and conclusionThis study will provide knowledge relevant to organizational practitioners and scholars who want to implement JC interventions with lasting effects. Although data collected following the group concept mapping procedure is self-reported and at risk of being simplified, the method allows for a structured conceptualization process integrating different perspectives and uncovering implicit knowledge making it suitable for studying complex phenomena. The results will not only enrich the current literature concerning the effectiveness of JC interventions but also be used to develop a practitioner-oriented toolkit outlining evidence-based recommendations concerning designing and implementing, as well as evaluating JC interventions.

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A last-in first-out stack data structure implemented in DNA.

Publications

A last-in first-out stack data structure implemented in DNA.

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