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Accessing Nystatin through Mariculture.

ABSTRACT: Understanding our oceans and their marine ecosystems has enabled the development of sustainable systems for mariculture. While the bulk of studies to date have focused on the production of food, its remarkable expanse has inspired the translation of other markets towards aquatic environments. This manuscript outlines an approach to pharmaceutical mariculture, by demonstrating a benchmark for future prototyping. Here, design, field evaluation and natural product chemistry are united to successfully produce nystatin at sea. This study begins by evaluating new designs for culture flasks, illustrating a next step towards developing self-contained bioreactors for culturing in marine environments. Through pilot studies, an underwater system was developed to cost effectively produce cultures that yielded 200 mg of nystatin per deployment. Overall, this study demonstrates the potential for the practical culturing of microbes in a marine environment and provides an important next step for the fledgling field of molecular mariculture.

SUBMITTER: La Clair JJ

PROVIDER: S-EPMC8708966 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Accessing human selenoproteins through chemical protein synthesis.

Project description:The human body contains 25 selenoproteins, which contain in their sequence the twenty-first encoded amino acid, selenocysteine. About a dozen of these proteins remain functionally uncharacterized or poorly studied. Challenges in accessing these selenoproteins using traditional recombinant expressions have prevented biological characterization thus far. Chemical protein synthesis has the potential to overcome these hurdles. Here we report the first total chemical syntheses of two human selenoproteins, selenoprotein M (SELM) and selenoprotein W (SELW). The synthesis of the more challenging protein SELM was enabled using recent advances in the field of selenocysteine chemistry. This approach allows the preparation of selenoproteins in milligram quantities and in homogenous form, which should open new horizons for future studies to pursue a fuller biological understanding of their role in health and disease.

| S-EPMC5364654 | biostudies-literature

Accessing 1,2-Substituted Cyclobutanes through 1,2-Azaborine Photoisomerization.

Project description:We provide a seminal example of the utility of the 1,2-azaborine motif as a 4C+1N+1B synthon in organic synthesis. Specifically, conditions for the practically scalable photoisomerization of 1,2-azaborine in a flow reactor are reported that furnish aminoborylated cyclobutane derivatives. The C-B bonds could also be functionalized to furnish a diverse set of highly substituted cyclobutanes.

| S-EPMC6917847 | biostudies-literature

SWS: accessing SRS sites contents through Web Services.

Project description:BackgroundWeb Services and Workflow Management Systems can support creation and deployment of network systems, able to automate data analysis and retrieval processes in biomedical research. Web Services have been implemented at bioinformatics centres and workflow systems have been proposed for biological data analysis. New databanks are often developed by taking into account these technologies, but many existing databases do not allow a programmatic access. Only a fraction of available databanks can thus be queried through programmatic interfaces. SRS is a well know indexing and search engine for biomedical databanks offering public access to many databanks and analysis tools. Unfortunately, these data are not easily and efficiently accessible through Web Services.ResultsWe have developed 'SRS by WS' (SWS), a tool that makes information available in SRS sites accessible through Web Services. Information on known sites is maintained in a database, srsdb. SWS consists in a suite of WS that can query both srsdb, for information on sites and databases, and SRS sites. SWS returns results in a text-only format and can be accessed through a WSDL compliant client. SWS enables interoperability between workflow systems and SRS implementations, by also managing access to alternative sites, in order to cope with network and maintenance problems, and selecting the most up-to-date among available systems.ConclusionsDevelopment and implementation of Web Services, allowing to make a programmatic access to an exhaustive set of biomedical databases can significantly improve automation of in-silico analysis. SWS supports this activity by making biological databanks that are managed in public SRS sites available through a programmatic interface.

| S-EPMC2323664 | biostudies-literature

Accessing Unusual Reactivity through Chelation-Promoted Bond Weakening.

Project description:Highly reducing Sm(II) reductants and protic ligands were used as a platform to ascertain the relationship between low-valent metal-protic ligand affinity and degree of ligand X-H bond weakening with the goal of forming potent proton-coupled electron transfer (PCET) reductants. Among the Sm(II)-protic ligand reductant systems investigated, the samarium dibromide N-methylethanolamine (SmBr2-NMEA) reagent system displayed the best combination of metal-ligand affinity and stability against H2 evolution. The use of SmBr2-NMEA afforded the reduction of a range of substrates that are typically recalcitrant to single-electron reduction including alkynes, lactones, and arenes as stable as biphenyl. Moreover, the unique role of NMEA as a chelating ligand for Sm(II) was demonstrated by the reductive cyclization of unactivated esters bearing pendant olefins in contrast to the SmBr2-water-amine system. Finally, the SmBr2-NMEA reagent system was found to reduce substrates analogous to key intermediates in the nitrogen fixation process. These results reveal SmBr2-NMEA to be a powerful reductant for a wide range of challenging substrates and demonstrate the potential for the rational design of PCET reagents with exceptionally weak X-H bonds.

| S-EPMC10249415 | biostudies-literature

Accessing genomic data through XML-based remote procedure calls.

Project description:As the amount of data in public genomic databases grows, interoperability among them is becoming an increasingly critical feature. The ability for automated systems to mine and integrate data will be crucial to extracting knowledge from sources of data whose volume far exceeds the capabilities of human researchers. The currently dominant paradigm of presenting information as Web pages and using hyperlinks to describe relationships between pieces of information favors usability, but makes interoperability and automated data exchange more difficult. In this paper we describe how SNPper, a web-based system for the retrieval and analysis of Single Nucleotide Polymorphisms (SNPs), was augmented with a Remote Procedure Call interface, allowing client applications to query our program for SNP data and to receive the response as an XML document. Data represented in this form can be easily parsed by the requesting program, and thus reused for other applications. In this paper we describe the implementation of the interface and we show examples of its usage in a number of existing applications.

| S-EPMC2244329 | biostudies-other

Accessing Mefenamic Acid Form II through High-Pressure Recrystallisation.

Project description:High-pressure crystallisation has been successfully used as an alternative technique to prepare Form II of a non-steroidal anti-inflammatory drug, mefenamic acid (MA). A single crystal of Form II, denoted as high-pressure Form II, was grown at 0.3 GPa from an ethanolic solution by using a diamond anvil cell. A comparison of the crystal structures shows that the efficient packing of molecules in Form II was enabled by the structural flexibility of MA molecules. Compression studies performed on a single crystal of Form I resulted in a 14% decrease of unit cell volume up to 2.5 GPa. No phase transition was observed up to this pressure. A reconstructive phase transition is required to induce conformational changes in the structure, which was confirmed by the results of crystallisation at high pressure.

| S-EPMC5489933 | biostudies-literature

Accessing Pluripotency from the Somatic Side

Project description:We report that Jdp2, Jhdm1b, Mkk6, Glis1, Nanog, Essrb and Sall4 (7F) convert MEFs to chimera competent iPSCs with fast kinetics. Time lapse microscopy reveal morphological changes distinct for 7F and Yamanaka factor (YF) reprogramming. Bulk transcriptomic analyses suggest that 7F and YF share 927 up and 548 down regulated genes, but differ in 1138 YF and 427 7F specifically activated genes. Single cell RNA sequencing reveals a fate path that can be further resolved into a cell fate continuum based on a MEF/ESC scoring system. A crossing point marks the transition in the continuum from somatic to pluripotent fates. By sampling the leading cells along this continuum, we identified transition stages marked by novel nu-clear factors and cell surface molecules. Our results reveal an efficient path to pluripotency and suggest that cell fate is governed by intrinsic fac-tors accessible by diverse approaches

2020-01-01 | GSE110208 | GEO

Accessing microfluidics through feature-based design software for 3D printing.

Project description:Additive manufacturing has been a cornerstone of the product development pipeline for decades, playing an essential role in the creation of both functional and cosmetic prototypes. In recent years, the prospects for distributed and open source manufacturing have grown tremendously. This growth has been enabled by an expanding library of printable materials, low-cost printers, and communities dedicated to platform development. The microfluidics community has embraced this opportunity to integrate 3D printing into the suite of manufacturing strategies used to create novel fluidic architectures. The rapid turnaround time and low cost to implement these strategies in the lab makes 3D printing an attractive alternative to conventional micro- and nanofabrication techniques. In this work, the production of multiple microfluidic architectures using a hybrid 3D printing-soft lithography approach is demonstrated and shown to enable rapid device fabrication with channel dimensions that take advantage of laminar flow characteristics. The fabrication process outlined here is underpinned by the implementation of custom design software with an integrated slicer program that replaces less intuitive computer aided design and slicer software tools. Devices are designed in the program by assembling parameterized microfluidic building blocks. The fabrication process and flow control within 3D printed devices were demonstrated with a gradient generator and two droplet generator designs. Precise control over the printing process allowed 3D microfluidics to be printed in a single step by extruding bridge structures to 'jump-over' channels in the same plane. This strategy was shown to integrate with conventional nanofabrication strategies to simplify the operation of a platform that incorporates both nanoscale features and 3D printed microfluidics.

| S-EPMC5875762 | biostudies-literature

Accessing scientific data through knowledge graphs with <i>Ontop</i>.

Project description:In this tutorial, we learn how to set up and exploit the virtual knowledge graph (VKG) approach to access data stored in relational legacy systems and to enrich such data with domain knowledge coming from different heterogeneous (biomedical) resources. The VKG approach is based on an ontology that describes a domain of interest in terms of a vocabulary familiar to the user and exposes a high-level conceptual view of the data. Users can access the data by exploiting the conceptual view, and in this way they do not need to be aware of low-level storage details. They can easily integrate ontologies coming from different sources and can obtain richer answers thanks to the interaction between data and domain knowledge.

| S-EPMC8515008 | biostudies-literature

Accessing the hidden majority of marine natural products through metagenomics.

Project description:Tiny marine animals represent an untapped reservoir for undiscovered, bioactive natural products. However, their small size and extreme chemical variability preclude traditional chemical approaches to discovering new bioactive compounds. Here, we use a metagenomic method to directly discover and rapidly access cyanobactin class natural products from these variable samples, and provide proof-of-concept for genome-based discovery and supply of marine natural products. We also address practical optimization of complex, multistep ribosomal peptide pathways in heterologous hosts, which is still very challenging. The resulting methods and concepts will be applicable to ribosomal peptide and other biosynthetic pathways.

| S-EPMC3397154 | biostudies-literature

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