scholarly journals Rapid Hyperpolarization and Purification of the Metabolite Fumarate in Aqueous Solution

2020 ◽  
Author(s):  
Stephan Knecht ◽  
John W. Blanchard ◽  
Danila Barskiy ◽  
Eleonora Cavallari ◽  
Laurynas Dagys ◽  
...  
Keyword(s):  
Nuclear Polarization ◽  
State Of The Art ◽  
Acid Precipitation ◽  
Metabolic Imaging ◽  
Reaction Conditions ◽  
Current State ◽  
Promising Agent ◽  
Aqueous Solvent ◽  
Cellular Necrosis

Hyperpolarized fumarate is a promising agent for carbon-13 magnetic resonance metabolic imaging of cellular necrosis. Molecular imaging applications require nuclear hyperpolarization to attain sufficient signal strength. Dissolution dynamic nuclear polarization is the current state-of-the-art methodology for hyperpolarizing fumarate, but this is expensive and relatively slow. Alternatively, this important biomolecule can be hyperpolarized in a cheap and convenient manner using parahydrogen-induced polarization. However, this process requires a chemical reaction, and the resulting hyperpolarized fumarate solutions are contaminated with the catalyst, unreacted reagents, and reaction side product molecules, and are hence unsuitable for use <i>in vivo</i>. In this work we show that the hyperpolarized fumarate can be purified from these contaminants by acid precipitation as a pure solid, and later redissolved at a chosen concentration in a clean aqueous solvent. Significant advances in the reaction conditions and reactor equipment allow us to form hyperpolarized fumarate at a concentration of several hundred millimolar, at <sup>13</sup>C polarization levels of 30-45%.

scholarly journals Rapid Hyperpolarization and Purification of the Metabolite Fumarate in Aqueous Solution

2020 ◽  
Author(s):  
Stephan Knecht ◽  
John W. Blanchard ◽  
Danila Barskiy ◽  
Eleonora Cavallari ◽  
Laurynas Dagys ◽  
...  
Keyword(s):  
Nuclear Polarization ◽  
State Of The Art ◽  
Acid Precipitation ◽  
Metabolic Imaging ◽  
Reaction Conditions ◽  
Current State ◽  
Promising Agent ◽  
Aqueous Solvent ◽  
Cellular Necrosis

Hyperpolarized fumarate is a promising agent for carbon-13 magnetic resonance metabolic imaging of cellular necrosis. Molecular imaging applications require nuclear hyperpolarization to attain sufficient signal strength. Dissolution dynamic nuclear polarization is the current state-of-the-art methodology for hyperpolarizing fumarate, but this is expensive and relatively slow. Alternatively, this important biomolecule can be hyperpolarized in a cheap and convenient manner using parahydrogen-induced polarization. However, this process requires a chemical reaction, and the resulting hyperpolarized fumarate solutions are contaminated with the catalyst, unreacted reagents, and reaction side product molecules, and are hence unsuitable for use <i>in vivo</i>. In this work we show that the hyperpolarized fumarate can be purified from these contaminants by acid precipitation as a pure solid, and later redissolved at a chosen concentration in a clean aqueous solvent. Significant advances in the reaction conditions and reactor equipment allow us to form hyperpolarized fumarate at a concentration of several hundred millimolar, at <sup>13</sup>C polarization levels of 30-45%.

scholarly journals Rapid hyperpolarization and purification of the metabolite fumarate in aqueous solution

2021 ◽  
Vol 118 (13) ◽  
pp. e2025383118
Author(s):  
Stephan Knecht ◽  
John W. Blanchard ◽  
Danila Barskiy ◽  
Eleonora Cavallari ◽  
Laurynas Dagys ◽  
...  
Keyword(s):  
Aqueous Solution ◽  
Nuclear Polarization ◽  
State Of The Art ◽  
Signal Strength ◽  
Acid Precipitation ◽  
Metabolic Imaging ◽  
Reaction Conditions ◽  
Current State ◽  
Aqueous Solvent

Hyperpolarized fumarate is a promising biosensor for carbon-13 magnetic resonance metabolic imaging. Such molecular imaging applications require nuclear hyperpolarization to attain sufficient signal strength. Dissolution dynamic nuclear polarization is the current state-of-the-art methodology for hyperpolarizing fumarate, but this is expensive and relatively slow. Alternatively, this important biomolecule can be hyperpolarized in a cheap and convenient manner using parahydrogen-induced polarization. However, this process requires a chemical reaction, and the resulting solutions are contaminated with the catalyst, unreacted reagents, and reaction side-product molecules, and are hence unsuitable for use in vivo. In this work we show that the hyperpolarized fumarate can be purified from these contaminants by acid precipitation as a pure solid, and later redissolved to a desired concentration in a clean aqueous solvent. Significant advances in the reaction conditions and reactor equipment allow for formation of hyperpolarized fumarate at 13C polarization levels of 30–45%.

scholarly journals In vivo interactome profiling by enzyme‐catalyzed proximity labeling

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yangfan Xu ◽  
Xianqun Fan ◽  
Yang Hu
Keyword(s):  
State Of The Art ◽  
Catalytic Efficiency ◽  
Biological Processes ◽  
Protein Protein Interaction ◽  
Current State ◽  
Protein Interactome ◽  
Potential Applications ◽  
Protein Protein Interaction Networks ◽  
Temporal And Spatial

AbstractEnzyme-catalyzed proximity labeling (PL) combined with mass spectrometry (MS) has emerged as a revolutionary approach to reveal the protein-protein interaction networks, dissect complex biological processes, and characterize the subcellular proteome in a more physiological setting than before. The enzymatic tags are being upgraded to improve temporal and spatial resolution and obtain faster catalytic dynamics and higher catalytic efficiency. In vivo application of PL integrated with other state of the art techniques has recently been adapted in live animals and plants, allowing questions to be addressed that were previously inaccessible. It is timely to summarize the current state of PL-dependent interactome studies and their potential applications. We will focus on in vivo uses of newer versions of PL and highlight critical considerations for successful in vivo PL experiments that will provide novel insights into the protein interactome in the context of human diseases.

scholarly journals Electro-Quasistatic Animal Body Communication for Untethered Rodent Biopotential Recording

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shreeya Sriram ◽  
Shitij Avlani ◽  
Matthew P. Ward ◽  
Shreyas Sen
Keyword(s):  
Lower Energy ◽  
Sensor Node ◽  
State Of The Art ◽  
The Body ◽  
Animal Body ◽  
Current State ◽  
Communication Modalities ◽  
First Time ◽  
Biopotential Recording

AbstractContinuous multi-channel monitoring of biopotential signals is vital in understanding the body as a whole, facilitating accurate models and predictions in neural research. The current state of the art in wireless technologies for untethered biopotential recordings rely on radiative electromagnetic (EM) fields. In such transmissions, only a small fraction of this energy is received since the EM fields are widely radiated resulting in lossy inefficient systems. Using the body as a communication medium (similar to a ’wire’) allows for the containment of the energy within the body, yielding order(s) of magnitude lower energy than radiative EM communication. In this work, we introduce Animal Body Communication (ABC), which utilizes the concept of using the body as a medium into the domain of untethered animal biopotential recording. This work, for the first time, develops the theory and models for animal body communication circuitry and channel loss. Using this theoretical model, a sub-inch$$^3$$ 3 [1″ × 1″ × 0.4″], custom-designed sensor node is built using off the shelf components which is capable of sensing and transmitting biopotential signals, through the body of the rat at significantly lower powers compared to traditional wireless transmissions. In-vivo experimental analysis proves that ABC successfully transmits acquired electrocardiogram (EKG) signals through the body with correlation $$>99\%$$ > 99 % when compared to traditional wireless communication modalities, with a 50$$\times$$ × reduction in power consumption.

scholarly journals Optimizing the Reaction Conditions for the Formation of Fumarate via Trans-Hydrogenation

2021 ◽  
Author(s):  
Laura Wienands ◽  
Franziska Theiß ◽  
James Eills ◽  
Lorenz Rösler ◽  
Stephan Knecht ◽  
...  
Keyword(s):  
Aqueous Solution ◽  
Thermal Equilibrium ◽  
Reaction Rate ◽  
Low Cost ◽  
Hydrogen Gas ◽  
Metabolic Imaging ◽  
Reaction Conditions ◽  
Precursor Molecule ◽  
Solution Preparation

AbstractParahydrogen-induced polarization is a hyperpolarization method for enhancing nuclear magnetic resonance signals by chemical reactions/interactions involving the para spin isomer of hydrogen gas. This method has allowed for biomolecules to be hyperpolarized to such a level that they can be used for real time in vivo metabolic imaging. One particularly promising example is fumarate, which can be rapidly and efficiently hyperpolarized at low cost by hydrogenating an acetylene dicarboxylate precursor molecule using parahydrogen. The reaction is relatively slow compared to the timescale on which the hyperpolarization relaxes back to thermal equilibrium, and an undesirable 2nd hydrogenation step can convert the fumarate into succinate. To date, the hydrogenation chemistry has not been thoroughly investigated, so previous work has been inconsistent in the chosen reaction conditions in the search for ever-higher reaction rate and yield. In this work we investigate the solution preparation protocols and the reaction conditions on the rate and yield of fumarate formation. We report conditions to reproducibly yield over 100 mM fumarate on a short timescale, and discuss aspects of the protocol that hinder the formation of fumarate or lead to irreproducible results. We also provide experimental procedures and recommendations for performing reproducible kinetics experiments in which hydrogen gas is repeatedly bubbled into an aqueous solution, overcoming challenges related to the viscosity and surface tension of the water.

scholarly journals In vitro and in vivo trematode models for chemotherapeutic studies

Parasitology ◽  
2009 ◽  
Vol 137 (3) ◽  
pp. 589-603 ◽  
Author(s):  
J. KEISER
Keyword(s):  
Liver Fluke ◽  
Fasciola Hepatica ◽  
State Of The Art ◽  
Parasitic Diseases ◽  
Current State ◽  
Food Borne ◽  
Essential Components ◽  
Discovery Pipeline

SUMMARYSchistosomiasis and food-borne trematodiases are chronic parasitic diseases affecting millions of people mostly in the developing world. Additional drugs should be developed as only few drugs are available for treatment and drug resistance might emerge. In vitro and in vivo whole parasite screens represent essential components of the trematodicidal drug discovery cascade. This review describes the current state-of-the-art of in vitro and in vivo screening systems of the blood fluke Schistosoma mansoni, the liver fluke Fasciola hepatica and the intestinal fluke Echinostoma caproni. Examples of in vitro and in vivo evaluation of compounds for activity are presented. To boost the discovery pipeline for these diseases there is a need to develop validated, robust high-throughput in vitro systems with simple readouts.

scholarly journals Joint epitope selection and spacer design for string-of-beads vaccines

2020 ◽  
Vol 36 (Supplement_2) ◽  
pp. i643-i650
Author(s):  
Emilio Dorigatti ◽  
Benjamin Schubert
Keyword(s):  
Antigen Processing ◽  
State Of The Art ◽  
Supplementary Information ◽  
Current State ◽  
Fixed Set ◽  
Epitope Selection ◽  
High Chance ◽  
Selection Of ◽  
Design Steps

Abstract Motivation Conceptually, epitope-based vaccine design poses two distinct problems: (i) selecting the best epitopes to elicit the strongest possible immune response and (ii) arranging and linking them through short spacer sequences to string-of-beads vaccines, so that their recovery likelihood during antigen processing is maximized. Current state-of-the-art approaches solve this design problem sequentially. Consequently, such approaches are unable to capture the inter-dependencies between the two design steps, usually emphasizing theoretical immunogenicity over correct vaccine processing, thus resulting in vaccines with less effective immunogenicity in vivo. Results In this work, we present a computational approach based on linear programming, called JessEV, that solves both design steps simultaneously, allowing to weigh the selection of a set of epitopes that have great immunogenic potential against their assembly into a string-of-beads construct that provides a high chance of recovery. We conducted Monte Carlo cleavage simulations to show that a fixed set of epitopes often cannot be assembled adequately, whereas selecting epitopes to accommodate proper cleavage requirements substantially improves their recovery probability and thus the effective immunogenicity, pathogen and population coverage of the resulting vaccines by at least 2-fold. Availability and implementation The software and the data analyzed are available at https://github.com/SchubertLab/JessEV. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Robotic automation of “blind” and two-photon targeted patch-clamp electrophysiology in vivo

2021 ◽  
Author(s):  
Gema Vera Gonzalez ◽  
Phatsimo Kgwarae ◽  
Luca Annecchino ◽  
Simon Schultz
Keyword(s):  
Patch Clamp ◽  
Review Paper ◽  
State Of The Art ◽  
Two Photon ◽  
Current State ◽  
Patch Clamp Electrophysiology ◽  
Robotic Automation

A review paper on the current state of the art in robotic automation of in vivo patch-clamp electrophysiology

Attenuation Estimation in Reflection: Progress and Prospects

1984 ◽  
Vol 6 (4) ◽  
pp. 349-395 ◽  
Author(s):  
J. Ophir ◽  
T. H. Shawker ◽  
N. F. Maklad ◽  
J. G. Miller ◽  
S. W. Flax ◽  
...  
Keyword(s):  
Time Domain ◽  
State Of The Art ◽  
Ultrasonic Attenuation ◽  
Clinical Results ◽  
Current State ◽  
Clinical Indications ◽  
Attenuation Estimation

This monograph presents a tutorial review of the current state-of-the-art in ultrasonic attenuation estimation in reflection. Clinical indications which provide the motivation for attempting in vivo attenuation estimation are discussed. Frequency and time domain techniques and their respective tradeoffs and problems are presented. Finally, current clinical results obtained with the various techniques are summarized and further areas of study are suggested.

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