scholarly journals A pipeline for making 31P NMR accessible for small- and large-scale lipidomics studies

2021 ◽  
Author(s):  
Samuel Furse ◽  
Huw E. L. Williams ◽  
Adam J. Watkins ◽  
Samuel Virtue ◽  
Antonio Vidal-Puig ◽  
...  
Keyword(s):  
Large Scale ◽  
A Priori ◽  
Structural Data ◽  
Mass Spectrometry Data ◽  
Head Group ◽  
Sample Extraction ◽  
Tools And Techniques ◽  
Scientific Questions ◽  
Insight Into ◽  
Detailed Molecular Analysis

AbstractDetailed molecular analysis is of increasing importance in research into the regulation of biochemical pathways, organismal growth and disease. Lipidomics in particular is increasingly sought after as it provides insight into molecular species involved in energy storage, signalling and fundamental cellular structures. This has led to the use of a range of tools and techniques to acquire lipidomics data. 31P NMR for lipidomics offers well-resolved head group/lipid class analysis, structural data that can be used to inform and strengthen interpretation of mass spectrometry data and part of a priori structural determination. In the present study, we codify the use of 31P NMR for lipidomics studies to make the technique more accessible to new users and more useful for a wider range of questions. The technique can be used in isolation (phospholipidomics) or as a part of determining lipid composition (lipidomics). We describe the process from sample extraction to data processing and analysis. This pipeline is important because it allows greater thoroughness in lipidomics studies and increases scope for answering scientific questions about lipid-containing systems.

scholarly journals A Pipeline for Making 31P NMR Accessible for Small- and Large-Scale Lipidomics Studies

2021 ◽  
Author(s):  
Samuel Furse ◽  
Huw Williams ◽  
Adam Watkins ◽  
Samuel Virtue ◽  
Antonio Vidal-Puig ◽  
...  
Keyword(s):  
Large Scale ◽  
31P Nmr ◽  
A Priori ◽  
Structural Data ◽  
Mass Spectrometry Data ◽  
Head Group ◽  
Sample Extraction ◽  
Tools And Techniques ◽  
Scientific Questions ◽  
Insight Into

Detailed molecular analysis is of increasing importance in research into the regulation of biochemical pathways, organismal growth and disease. Lipidomics in particular is increasingly sought after as it provides insight into molecular species involved in energy storage, signalling and fundamental cellular structures. This has led to the use of a range of tools and techniques to acquire lipidomics data. 31P NMR for lipidomics offers well-resolved head group/lipid class analysis, structural data that can be used to inform and strengthen interpretation of mass spectrometry data and part of structural determination a priori. In the present study, we codify the use of 31P NMR for lipidomics to make the technique more accessible to new users and more useful for a wider range of studies. We describe the process from sample extraction to data processing and analysis. This pipeline is important because it allows greater thoroughness in lipidomics studies and increases scope for answering scientific questions about lipid systems.

scholarly journals A Pipeline for Making 31P NMR Accessible for Small- and Large-Scale Lipidomics Studies

2021 ◽  
Author(s):  
Samuel Furse ◽  
Huw Williams ◽  
Adam Watkins ◽  
Samuel Virtue ◽  
Antonio Vidal-Puig ◽  
...  
Keyword(s):  
Large Scale ◽  
31P Nmr ◽  
A Priori ◽  
Structural Data ◽  
Mass Spectrometry Data ◽  
Head Group ◽  
Sample Extraction ◽  
Tools And Techniques ◽  
Scientific Questions ◽  
Insight Into

Detailed molecular analysis is of increasing importance in research into the regulation of biochemical pathways, organismal growth and disease. Lipidomics in particular is increasingly sought after as it provides insight into molecular species involved in energy storage, signalling and fundamental cellular structures. This has led to the use of a range of tools and techniques to acquire lipidomics data. 31P NMR for lipidomics offers well-resolved head group/lipid class analysis, structural data that can be used to inform and strengthen interpretation of mass spectrometry data and part of structural determination a priori. In the present study, we codify the use of 31P NMR for lipidomics to make the technique more accessible to new users and more useful for a wider range of studies. We describe the process from sample extraction to data processing and analysis. This pipeline is important because it allows greater thoroughness in lipidomics studies and increases scope for answering scientific questions about lipid systems.

scholarly journals Jumping Ahead with Sleeping Beauty: Mechanistic Insights into Cut-and-Paste Transposition

Viruses ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 76
Author(s):  
Matthias T. Ochmann ◽  
Zoltán Ivics
Keyword(s):  
Genetic Engineering ◽  
Structural Data ◽  
Sleeping Beauty ◽  
Preclinical Studies ◽  
Gene Vector ◽  
Functional Information ◽  
Vector Systems ◽  
Novel Variants ◽  
Insight Into ◽  
Cellular Genome

Sleeping Beauty (SB) is a transposon system that has been widely used as a genetic engineering tool. Central to the development of any transposon as a research tool is the ability to integrate a foreign piece of DNA into the cellular genome. Driven by the need for efficient transposon-based gene vector systems, extensive studies have largely elucidated the molecular actors and actions taking place during SB transposition. Close transposon relatives and other recombination enzymes, including retroviral integrases, have served as useful models to infer functional information relevant to SB. Recently obtained structural data on the SB transposase enable a direct insight into the workings of this enzyme. These efforts cumulatively allowed the development of novel variants of SB that offer advanced possibilities for genetic engineering due to their hyperactivity, integration deficiency, or targeting capacity. However, many aspects of the process of transposition remain poorly understood and require further investigation. We anticipate that continued investigations into the structure–function relationships of SB transposition will enable the development of new generations of transposition-based vector systems, thereby facilitating the use of SB in preclinical studies and clinical trials.

scholarly journals Antiviral Resistance against Viral Mutation: Praxis and Policy for SARS-CoV-2

2021 ◽  
Vol 9 (1) ◽  
pp. 81-89
Author(s):  
Robert Penner
Keyword(s):  
Free Energy ◽  
Vaccine Development ◽  
A Priori ◽  
Structural Data ◽  
Medical Sciences ◽  
Spike Glycoprotein ◽  
Mutagenic Potential ◽  
Viral Mutation ◽  
Novel Method ◽  
Antiviral Targets

Abstract Tools developed by Moderna, BioNTech/Pfizer, and Oxford/Astrazeneca, among others, provide universal solutions to previously problematic aspects of drug or vaccine delivery, uptake and toxicity, portending new tools across the medical sciences. A novel method is presented based on estimating protein backbone free energy via geometry to predict effective antiviral targets, antigens and vaccine cargos that are resistant to viral mutation. This method is reviewed and reformulated in light of the recent proliferation of structural data on the SARS-CoV-2 spike glycoprotein and its mutations in multiple lineages. Key findings include: collections of mutagenic residues reoccur across strains, suggesting cooperative convergent evolution; most mutagenic residues do not participate in backbone hydrogen bonds; metastability of the glyco-protein limits the change of free energy through mutation thereby constraining selective pressure; and there are mRNA or virus-vector cargos targeting low free energy peptides proximal to conserved high free energy peptides providing specific recipes for vaccines with greater specificity than the full-spike approach. These results serve to limit peptides in the spike glycoprotein with high mutagenic potential and thereby provide a priori constraints on viral and attendant vaccine evolution. Scientific and regulatory challenges to nucleic acid therapeutic and vaccine development and deployment are finally discussed.

scholarly journals Geo-Spatial Analysis of Population Density and Annual Income to Identify Large-Scale Socio-Demographic Disparities

2021 ◽  
Vol 10 (7) ◽  
pp. 432
Author(s):  
Nicolai Moos ◽  
Carsten Juergens ◽  
Andreas P. Redecker
Keyword(s):  
Population Density ◽  
Large Scale ◽  
Methodological Approach ◽  
Spatial Relationship ◽  
Postal Code ◽  
Annual Income ◽  
Choropleth Maps ◽  
Clustering Approach ◽  
Relationship Of ◽  
Insight Into

This paper describes a methodological approach that is able to analyse socio-demographic and -economic data in large-scale spatial detail. Based on the two variables, population density and annual income, one investigates the spatial relationship of these variables to identify locations of imbalance or disparities assisted by bivariate choropleth maps. The aim is to gain a deeper insight into spatial components of socioeconomic nexuses, such as the relationships between the two variables, especially for high-resolution spatial units. The used methodology is able to assist political decision-making, target group advertising in the field of geo-marketing and for the site searches of new shop locations, as well as further socioeconomic research and urban planning. The developed methodology was tested in a national case study in Germany and is easily transferrable to other countries with comparable datasets. The analysis was carried out utilising data about population density and average annual income linked to spatially referenced polygons of postal codes. These were disaggregated initially via a readapted three-class dasymetric mapping approach and allocated to large-scale city block polygons. Univariate and bivariate choropleth maps generated from the resulting datasets were then used to identify and compare spatial economic disparities for a study area in North Rhine-Westphalia (NRW), Germany. Subsequently, based on these variables, a multivariate clustering approach was conducted for a demonstration area in Dortmund. In the result, it was obvious that the spatially disaggregated data allow more detailed insight into spatial patterns of socioeconomic attributes than the coarser data related to postal code polygons.

Exploring genomes with a game engine

2014 ◽  
Vol 169 ◽  
pp. 443-453 ◽  
Author(s):  
Jeremiah J. Shepherd ◽  
Lingxi Zhou ◽  
William Arndt ◽  
Yan Zhang ◽  
W. Jim Zheng ◽  
...  
Keyword(s):  
Real Time ◽  
Video Game ◽  
Linear Structure ◽  
Structural Data ◽  
Game Engine ◽  
3D Genome ◽  
Genome Viewer ◽  
A Genome ◽  
Visualization Techniques ◽  
Insight Into

More and more evidence indicates that the 3D conformation of eukaryotic genomes is a critical part of genome function. However, due to the lack of accurate and reliable 3D genome structural data, this information is largely ignored and most of these studies have to use information systems that view the DNA in a linear structure. Visualizing genomes in real time 3D can give researchers more insight, but this is fraught with hardware limitations since each element contains vast amounts of information that cannot be processed on the fly. Using a game engine and sophisticated video game visualization techniques enables us to construct a multi-platform real-time 3D genome viewer. The game engine-based viewer achieves much better rendering speed and can handle much larger amounts of data compared to our previous implementation using OpenGL. Combining this viewer with 3D genome models from experimental data could provide unprecedented opportunities to gain insight into the conformation–function relationships of a genome.

scholarly journals Structure of a canonical RNase YoeB bound to the ribosome

2014 ◽  
Vol 70 (a1) ◽  
pp. C207-C207
Author(s):  
Yun Chen ◽  
Shu Feng ◽  
Katsuhiko Kamada ◽  
Han Wang ◽  
Kai Tang ◽  
...  
Keyword(s):  
Specific Activity ◽  
Base Catalysis ◽  
Mass Spectrometry Data ◽  
Catalytic Core ◽  
General Base ◽  
Rna Hydrolysis ◽  
70S Ribosome ◽  
A Site ◽  
Insight Into

As a typical endoribonuclease, YoeB mediates cellular adaptation in diverse bacteria by degrading mRNAs on its activation. Although the catalytic core of YoeB is thought to be identical to well-studied nucleases, this enzyme specifically targets mRNA substrates that are associated with ribosomes in vivo. However, the molecular mechanism of mRNA recognition and cleavage by YoeB, and the requirement of ribosome for its optimal activity, largely remain elusive. Here, we report the structure of YoeB bound to 70S ribosome in pre-cleavage state, revealing that both the 30S and 50S subunits participate in YoeB binding. The mRNA is recognized by the catalytic core of YoeB, of which the general base/acid (Glu46/His83) are within hydrogen-bonding distance to their reaction atoms, demonstrating an active conformation of YoeB on ribosome. Also, the mRNA orientation involves the universally conserved A1493 and G530 of 16S rRNA. In addition, mass spectrometry data indicated that YoeB cleaves mRNA following the second position at the A-site codon, resulting in a final product with a 3'–phosphate at the newly formed 3' end. Our results demonstrate a classical acid-base catalysis for YoeB-mediated RNA hydrolysis and provide insight into how the ribosome is essential for its specific activity.

scholarly journals Metachronal waves in magnetic micro-robotic paddles for artificial cilia

2021 ◽  
Vol 2 (1) ◽  
Author(s):  
Matthew T. Bryan ◽  
Elizabeth L. Martin ◽  
Aleksandra Pac ◽  
Andrew D. Gilbert ◽  
Feodor Y. Ogrin
Keyword(s):  
Large Scale ◽  
Point Of Care ◽  
Hydrodynamic Response ◽  
Flow Speeds ◽  
Break Time ◽  
Large Scale Manufacture ◽  
Fresh Insight ◽  
Metachronal Waves ◽  
Insight Into ◽  
Phase Differences

AbstractBiological cilia generate fluid movement within viscosity-dominated environments using beating motions that break time-reversal symmetry. This creates a metachronal wave, which enhances flow efficiency. Artificially mimicking this behaviour could improve microfluidic point-of-care devices, since viscosity-dominated fluid dynamics impede fluid flow and mixing of reagents, limiting potential for multiplexing diagnostic tests. However, current biomimicry schemes require either variation in the hydrodynamic response across a cilia array or a complex magnetic anisotropy configuration to synchronise the actuation sequence with the driving field. Here, we show that simple modifications to the structural design introduce phase differences between individual actuators, leading to the spontaneous formation of metachronal waves. This generates flow speeds of up to 16 μm/s as far as 675 μm above the actuator plane. By introducing metachronal waves through lithographic structuring, large scale manufacture becomes feasible. Additionally, by demonstrating that metachronal waves emerge from non-uniformity in internal structural mechanics, we offer fresh insight into the mechanics of cilia coordination.

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