Monday, January 30, 2017

Studies on the MxiH protein in T3SS needles using DNP-enhanced ssNMR spectroscopy #DNPNMR


Fricke, P., et al., Studies on the MxiH protein in T3SS needles using DNP-enhanced ssNMR spectroscopy. ChemPhysChem, 2014. 15(1): p. 57-60.


Bacterial T3SS needles formed by the protein MxiH are studied using DNP-enhanced ssNMR spectroscopy at 14.1 T (600 MHz). This technique provides spectra of good resolution, allowing us to draw conclusions about the protein dynamics. With the obtained signal enhancement, samples of limited quantity now get within reach of ssNMR studies.

Sunday, January 29, 2017

[NMR] Postdoc position on parahydrogen-enhanced NMR available in the Levitt group

From the Ampere Magnetic Resonance List


A 2-year postdoc position on parahydrogen-enhanced NMR is available in the Levitt group. For details, and to apply, see
https://jobs.soton.ac.uk/Vacancy.aspx?id=15204&forced=1

Malcolm

------------------------------------
Malcolm Levitt
School of Chemistry
Room 27:2026
University of Southampton
Southampton SO17 1BJ
England.

tel. +44 23 8059 6753
fax: +44 23 8059 3781
iPhone: +44 77 7078 2024

mhl@soton.ac.uk<mailto:mhl@soton.ac.uk>
work: http://www.southampton.ac.uk/magres/about/staff/levitt.page?
personal: http://www.malcolmhlevitt.com
music: sevenstones.bandcamp.com<http://sevenstones.bandcamp.com>
*******************************************


====================================
This is the AMPERE MAGNETIC RESONANCE mailing list:
http://www.drorlist.com/nmrlist.html

NMR web database:
http://www.drorlist.com/nmr.html

Friday, January 27, 2017

High resolution observed in 800 MHz DNP spectra of extremely rigid type III secretion needles #DNPNMR


Fricke, P., et al., High resolution observed in 800 MHz DNP spectra of extremely rigid type III secretion needles. J Biomol NMR, 2016. 65(3-4): p. 121-6.


The cryogenic temperatures at which dynamic nuclear polarization (DNP) solid-state NMR experiments need to be carried out cause line-broadening, an effect that is especially detrimental for crowded protein spectra. By increasing the magnetic field strength from 600 to 800 MHz, the resolution of DNP spectra of type III secretion needles (T3SS) could be improved by 22 %, indicating that inhomogeneous broadening is not the dominant effect that limits the resolution of T3SS needles under DNP conditions. The outstanding spectral resolution of this system under DNP conditions can be attributed to its low overall flexibility.

Wednesday, January 25, 2017

Temperature dependence of cross-effect dynamic nuclear polarization in rotating solids: advantages of elevated temperatures #DNPNMR


Geiger, M.A., et al., Temperature dependence of cross-effect dynamic nuclear polarization in rotating solids: advantages of elevated temperatures. Phys. Chem. Chem. Phys., 2016. 18(44): p. 30696-30704.


Dynamic nuclear polarization exploits electron spin polarization to boost signal-to-noise in magic-angle-spinning (MAS) NMR, creating new opportunities in materials science, structural biology, and metabolomics studies. Since protein NMR spectra recorded under DNP conditions can show improved spectral resolution at 180-200 K compared to 110 K, we investigate the effects of AMUPol and various deuterated TOTAPOL isotopologues on sensitivity and spectral resolution at these temperatures, using proline and reproducibly prepared SH3 domain samples. The TOTAPOL deuteration pattern is optimized for protein DNP MAS NMR, and signal-to-noise per unit time measurements demonstrate the high value of TOTAPOL isotopologues for Protein DNP MAS NMR at 180-200 K. The combined effects of enhancement, depolarization, and proton longitudinal relaxation are surprisingly sample-specific. At 200 K, DNP on SH3 domain standard samples yields a 15-fold increase in signal-to-noise over a sample without radicals. 2D and 3D NCACX/NCOCX spectra were recorded at 200 K within 1 and 13 hours, respectively. Decreasing enhancements with increasing 2H-content at the CH2 sites of the TEMPO rings in CD3-TOTAPOL highlight the importance of protons in a sphere of 4-6 A around the nitroxyl group, presumably for polarization pickup from electron spins.






Tuesday, January 24, 2017

[NMR] Postdoc position at Univ. Lille, France, on high-field solid-state NMR of low-gamma quadrupolar nuclei in materials

From the Ampere Magnetic Resonance List



Postdoc position at Univ. Lille, France, on high-field solid-state NMR of low-gamma quadrupolar nuclei in materials

Project PIs: Laurent Delevoye, Olivier Lafon

Project objectives: Quadrupolar nuclei with gyromagnetic ratio lower than that of 15N nucleus represent about 40% of NMR active nuclei. Many important chemical elements, such as Mo, Zn, Zr, Ti or Mg, are only observable through these low-gamma quadrupolar nuclei. This project aims at developing methods for the observation of these isotopes and applying them for the structural study of hybrid materials. This project will take advantage of the use of Lille high-field solid-state NMR spectrometers (800 and 900 MHz), which are equipped with specific probes for the detection of low-gamma nuclei.

Hosts and research infrastructure: Lille is vibrant city, imbued with a rich history. It is located in the middle of northwestern Europe (only 30 min by high-speed trains from Brussels, 1h from Paris and 1h30 from London). Lille is a leading center for magnetic resonance. Lille magnetic resonance facility includes 800 and 900 MHz NMR spectrometers for the study of solids. It has also been selected to host the first 1.2 GHz NMR spectrometer to be installed in France.

The applicant: You hold a PhD degree in physics, chemistry or material sciences and you have first-author publications in peer-reviewed journals. Other requirements are good skills in written and spoken English. The successful applicant will be given the opportunity to work in an exciting environment with national and international collaborations. 

Interested candidates should send his/her CV with a covering letter (one single PDF) before Feb. 3, 2017 to Laurent Delevoye, laurent.delevoye@ensc-lille.fr and Olivier Lafon, olivier.lafon@univ-lille1.fr

====================================
This is the AMPERE MAGNETIC RESONANCE mailing list:

NMR web database:

Monday, January 23, 2017

Application of flow sensitive gradients for improved measures of metabolism using hyperpolarized (13) c MRI


Gordon, J.W., et al., Application of flow sensitive gradients for improved measures of metabolism using hyperpolarized (13) c MRI. Magn Reson Med, 2016. 75(3): p. 1242-8.


PURPOSE: To develop the use of bipolar gradients to suppress partial-volume and flow-related artifacts from macrovascular, hyperpolarized spins. THEORY AND METHODS: Digital simulations were performed over a range of spatial resolutions and gradient strengths to determine the optimal bipolar gradient strength and duration to suppress flowing spins while minimizing signal loss from static tissue. In vivo experiments were performed to determine the efficacy of this technique to suppress vascular signal in the study of hyperpolarized [1-(13)C]pyruvate renal metabolism. RESULTS: Digital simulations showed that in the absence of bipolar gradients, partial-volume artifacts from the vasculature were still present, causing underestimation of the apparent reaction rate of pyruvate to lactate (kP). The addition of a bipolar gradient with b = 32 s/mm(2) sufficiently suppressed the vascular signal without a substantial decrease in signal from static tissue. In vivo results corroborate digital simulations, with similar peak lactate signal to noise ratio (SNR) but substantially different kP in the presence of bipolar gradients. CONCLUSION: The proposed approach suppresses signal from flowing spins while minimizing signal loss from static tissue, removing contaminating signal from the vasculature and increasing kinetic modeling accuracy without substantially sacrificing SNR or temporal resolution.

Friday, January 20, 2017

Quantification of rate constants for successive enzymatic reactions with DNP hyperpolarized MR


Allouche-Arnon, H., et al., Quantification of rate constants for successive enzymatic reactions with DNP hyperpolarized MR. NMR Biomed, 2014. 27(6): p. 656-62.


A kinetic model is provided to obtain reaction rate constants in successive enzymatic reactions that are monitored using NMR spectroscopy and hyperpolarized substrates. The model was applied for simulation and analysis of the successive oxidation of choline to betaine aldehyde, and further to betaine, by the enzyme choline oxidase. This enzymatic reaction was investigated under two different sets of conditions: two different choline molecular probes were used, [1,1,2,2-D4 , 1-(13) C]choline chloride and [1,1,2,2-D4 , 2-(13) C]choline chloride, in different MR systems (clinical scanner and high-resolution spectrometer), as well as in different reactors and reaction volumes (4.8 and 0.7 mL). The kinetic analysis according to the model yielded similar results in both set-ups, supporting the robustness of the model. This was achieved despite the complex and negating influences of reaction kinetics and polarization decay, and in the presence of uncontrolled mixing characteristics, which may introduce uncertainties in both effective timing and effective pulses. The ability to quantify rate constants using hyperpolarized MR in the first seconds of consecutive enzyme activity is important for further development of the utilization of dynamic nuclear polarization-MR for biological determinations.

Wednesday, January 18, 2017

Hyperpolarized 13C NMR studies of glucose metabolism in living breast cancer cell cultures


Harris, T., H. Degani, and L. Frydman, Hyperpolarized 13C NMR studies of glucose metabolism in living breast cancer cell cultures. NMR Biomed, 2013. 26(12): p. 1831-43.


The recent development of dissolution dynamic nuclear polarization (DNP) gives NMR the sensitivity to follow metabolic processes in living systems with high temporal resolution. In this article, we apply dissolution DNP to study the metabolism of hyperpolarized U-(13)C,(2)H7-glucose in living, perfused human breast cancer cells. Spectrally selective pulses were used to maximize the signal of the main product, lactate, whilst preserving the glucose polarization; in this way, both C1-lactate and C3-lactate could be observed with high temporal resolution. The production of lactate by T47D breast cancer cells can be characterized by Michaelis-Menten-like kinetics, with K(m) = 3.5 +/- 1.5 mM and V(max) = 34 +/- 4 fmol/cell/min. The high sensitivity of this method also allowed us to observe and quantify the glycolytic intermediates dihydroxyacetone phosphate and 3-phosphoglycerate. Even with the enhanced DNP signal, many other glycolytic intermediates could not be detected directly. Nevertheless, by applying saturation transfer methods, the glycolytic intermediates glucose-6-phosphate, fructose-6-phosphate, fructose-1,6-bisphosphate, glyceraldehyde-3-phosphate, phosphoenolpyruvate and pyruvate could be observed indirectly. This method shows great promise for the elucidation of the distinctive metabolism and metabolic control of cancer cells, suggesting multiple ways whereby hyperpolarized U-(13)C,(2)H7-glucose NMR could aid in the diagnosis and characterization of cancer in vivo.

Tuesday, January 17, 2017

[NMR] PhD student position in hyperpolarized MRI of stroke

From the Ampere Magnetic Resonance List



A PhD student position funded by the Swiss National Science Foundation (SNSF) is available on Hyperpolarized MRI of stroke and neuroprotection. 


The project is a collaboration between the School of Health Sciences – Geneva, the Laboratory for Functional and Metabolic Imaging – EPFL and the Stroke Laboratory – CHUV.

The overall goal of the thesis is to study the neuroprotection mechanisms of lactate in ischemic stroke using hyperpolarized MRI in a mouse stroke model (MCAO). The project involves optimizing and applying MR tools for hyperpolarized metabolic imaging including hyperpolarization, pulse sequences and protocols.

The project has access to MRI scanners (preclinical 9.4T/ 14T/ 0.1T and human scanner 3T/ 7T), custom-design Dissolution - DNP polarizers (5T and 7T), a custom-design spin exchange optical pumping set-up and state of the art facilities for rodent surgery, molecular biology, biochemistry, and behavioral studies.

The successful candidate will have a strong interest in biomedical applications, be able to work independently in a multidisciplinary team; get acquainted with new methods quickly, and be willing to work with experimental hardware and with animals. With a master or equivalent, preferably in MR physics, biomedical imaging, biomedical engineering or related field, the candidate should have good communication skills and programming experience with matlab and/or C/C++.

French speaking proficiency and experience with MR sequence programming and signal/image processing is a plus. The project involves regular travels between Lausanne and Geneva.

Applicants should send by email a CV, motivation statement, master final marks, publications if any and references (with e-mail addresses) to: 



____________________________
Mor Mishkovsky, PhD
Phone: +41-(0)21-69-30590
Laboratory for Functional and Metabolic Imaging (LIFMET)
Ecole Polytechnique Fédérale de Lausanne (EPFL)
EPFL SB IPHYS LIFMET
CH F1 626 (Bâtiment CH)
Station 6
CH-1015 Lausanne (VD)
Switzerland

====================================
This is the AMPERE MAGNETIC RESONANCE mailing list:

NMR web database:

Monday, January 16, 2017

Dynamic nuclear polarisation via the integrated solid effect I: theory #DNPNMR


Henstra, A. and W.T. Wenckebach, Dynamic nuclear polarisation via the integrated solid effect I: theory. Mol. Phys., 2013. 112(13): p. 1761-1772.


In the hyperpolarisation method known as dynamic nuclear polarisation (DNP), a small amount of unpaired electron spins is added to the sample containing the nuclear spins and the polarisation of these unpaired electron spins is transferred to the nuclear spins by means of a microwave field. Traditional DNP uses weak continuous wave (CW) microwave fields, so perturbation methods can be used to calculate the polarisation transfer. A much faster transfer of the electron spin polarisation is obtained with the integrated solid effect (ISE) which uses strong pulsed microwave fields. As in nuclear orientation via electron spin locking, the polarisation transfer is coherent, similar to the coherence transfer between nuclear spins. This paper presents a theoretical approach to calculate this polarisation transfer. ISE is successfully used for a fast polarisation transfer from short-lived photo-excited triplet states to the surrounding nuclear spins in molecular crystals. These triplet states are strongly aligned in the photo-excitation process and do not require the low temperatures and strong magnetic fields needed to polarise the electron spins in traditional DNP. In the following paper, the theory is applied to the system naphthalene-h8 doped with pentacene-d14 which provides the photo-excited triplet states, and compared with experimental results.

Friday, January 13, 2017

Insight into the Supramolecular Architecture of Intact Diatom Biosilica from DNP-Supported Solid-State NMR Spectroscopy #DNPNMR


Jantschke, A., et al., Insight into the Supramolecular Architecture of Intact Diatom Biosilica from DNP-Supported Solid-State NMR Spectroscopy. Angew Chem Int Ed Engl, 2015. 54(50): p. 15069-73.


Diatom biosilica is an inorganic/organic hybrid with interesting properties. The molecular architecture of the organic material at the atomic and nanometer scale has so far remained unknown, in particular for intact biosilica. A DNP-supported ssNMR approach assisted by microscopy, MS, and MD simulations was applied to study the structural organization of intact biosilica. For the first time, the secondary structure elements of tightly biosilica-associated native proteins in diatom biosilica were characterized in situ. Our data suggest that these proteins are rich in a limited set of amino acids and adopt a mixture of random-coil and beta-strand conformations. Furthermore, biosilica-associated long-chain polyamines and carbohydrates were characterized, thereby leading to a model for the supramolecular organization of intact biosilica.

[NMR] MOOC on NMR, Feb. 20 to Apr. 17, 2017

From the Ampere Magnetic Resonance List



Dear colleagues,

In 2015, the Massive Open Online Course (MOOC) “Nuclear Magnetic Resonance (NMR), a Compass to Nanoworld” hosted on the FUN platform was one of the first MOOCs covering the subject of NMR.

It is our great pleasure to announce that the second! offering of this MOOC is now open for free registration. 

This MOOC in English aims at providing the basic knowledge about NMR and an overview of its applications to students and professionals who want to enter this field.

Topics to be covered include:

• Basic principles and practice of NMR spectroscopy;
• Solution NMR of small molecules;
• NMR of proteins and sugars;
• Basic principles and practice of solid-state NMR spectro scopy;
• NMR characterization of materials (glasses, heterogeneous catalysts, battery materials).

The courses will be held from February 20 to April 17, 2017. For this course, about 2-3 hours of work per week are expected. MOOC participants will learn through video lectures and online discussions with peers and professors. The acquired knowledge will be tested through weekly quizzes.

This course does not require previous knowledge about NMR spectroscopy. Nevertheless, the participants should have a background in basic chemistry (chemical elements, molecular structure) and in basic physics (magnetism, basic spectroscopy).

The teachers of this MOOC are Olivier Lafon (coordinator), Cédric Lion, Emmanuel Maes, Frédérique Pourpoint, Robert Schneider and Julien Trébosc. They belong to the University of Lille and the CNRS. The University of Lille is part o f the French network of high-field NMR facilities (http://www.ir-rmn.f! r/) and hosts 800 and 900 MHz NMR spectrometers for the study of liquids and solids. It has also been selected to host the first 1.2 GHz NMR spectrometer to be installed in France. 

Please distribute this announcement to your students as well as to your colleagues who may be interested.

If you are interested, please register through the website 
You can already watch the MOOC trailer on this website. 

With kind regards,

Olivier Lafon, Cedric Lion, Emmanuel Maes, Frederique Pourpoint, Robert Schneider and Julien Trebosc

-- 
________________________________________________________________
Olivier Lafon
Professor
Department of chemistry
University of Lille – Institut Universitaire de France
F-59652, Villeneuve d'Ascq, Cedex, France
Tel: 33 3 20 43 41 43 Fax : 33 3 20 43 68 14

____________________________________________________ ___________ 

====================================
This is the AMPERE MAGNETIC RESONANCE mailing list:

NMR web database:

Wednesday, January 11, 2017

DNP-Enhanced Ultrawideline Solid-State NMR Spectroscopy: Studies of Platinum in Metal-Organic Frameworks #DNPNMR


Kobayashi, T., et al., DNP-Enhanced Ultrawideline Solid-State NMR Spectroscopy: Studies of Platinum in Metal-Organic Frameworks. J Phys Chem Lett, 2016. 7(13): p. 2322-7.


Ultrawideline dynamic nuclear polarization (DNP)-enhanced (195)Pt solid-state NMR (SSNMR) spectroscopy and theoretical calculations are used to determine the coordination of atomic Pt species supported within the pores of metal-organic frameworks (MOFs). The (195)Pt SSNMR spectra, with breadths reaching 10000 ppm, were obtained by combining DNP with broadbanded cross-polarization and CPMG acquisition. Although the DNP enhancements in static samples are lower than those typically observed under magic-angle spinning conditions, the presented measurements would be very challenging using the conventional SSNMR methods. The DNP-enhanced ultrawideline NMR spectra served to separate signals from cis- and trans-coordinated atomic Pt(2+) species supported on the UiO-66-NH2 MOF. Additionally, the data revealed a dominance of kinetic effects in the formation of Pt(2+) complexes and the thermodynamic effects in their reduction to nanoparticles. A single cis-coordinated Pt(2+) complex was confirmed in MOF-253.

Tuesday, January 10, 2017

[NMR] Faculty Position in NMR

From the Ampere Magnetic Resonance List




Dear Colleagues

please note that the Chemistry Department of the Technical University of Dortmund has an open faculty position in bimolecular NMR at the full professor level (W3). Details are available at


or from the head of the search committee, Prof. Roland Winter <roland.winter@tu-dortmund.de>.

Please forward this information to any suitable candidates.

Sincerely,
Dieter Suter


____________________________________________________________________________
Dieter Suter | Tel: (+49 231) 755 3512
Fakultät Physik | Fax: (+49 231) 755 3509
Technische Universität Dortmund |
D-44221 Dortmund | e-mail: Dieter.Suter@tu-dortmund.de
____________________________________________________________________________

Monday, January 9, 2017

19F Dynamic Nuclear Polarization and SEM in Suspensions Consisting of Fluorobenzene Derivatives and Asphaltene Extracted from MC-800 Liquid Asphalt #DNPNMR


Kirimli, H.E. and H. Ovalioglu, 19F Dynamic Nuclear Polarization and SEM in Suspensions Consisting of Fluorobenzene Derivatives and Asphaltene Extracted from MC-800 Liquid Asphalt. Journal of Dispersion Science and Technology, 2014. 35(2): p. 255-264.


A variety of analytical techniques, such as scanning electron microscopy and 19F dynamic nuclear polarization (DNP) methods, are applied to characterize asphaltene extracted from MC-800 liquid asphalt in fluorobenzene derivatives at 1.53 mT and at room temperature. Different solvents show variable affinities for the asphaltene surface. The low field EPR spectrum of the asphaltene/hexafluorobenzene sample was recorded. The DNP parameters were determined. Additionally, the interactions between the nuclei of the solvent and the electrons delocalized on the asphaltene are interpreted. Not only dipolar but also scalar interactions between the nuclear spin and the electron spin were found.

Friday, January 6, 2017

Rational design of dinitroxide biradicals for efficient cross-effect dynamic nuclear polarization #DNPNMR


Kubicki, D.J., et al., Rational design of dinitroxide biradicals for efficient cross-effect dynamic nuclear polarization. Chem. Sci., 2016. 7(1): p. 550-558.


A series of 37 dinitroxide biradicals have been prepared and their performance studied as polarizing agents in cross-effect DNP NMR experiments at 9.4 T and 100 K in 1,1,2,2-tetrachloroethane (TCE). We observe that in this regime the DNP performance is strongly correlated with the substituents on the polarizing agents, and electron and nuclear spin relaxation times, with longer relaxation times leading to better enhancements. We also observe that deuteration of the radicals generally leads to better DNP enhancement but with longer build-up time. One of the new radicals introduced here provides the best performance obtained so far under these conditions.

[NMR] Two Research Fellowships in Southampton, UK, with deadline 19 Jan 2017

From the Ampere Magnetic Resonance List


Dear Colleagues,

There are two open Research Fellowships in Nuclear Magnetic Resonance in my group (http://www.southampton.ac.uk/chemistry/about/staff/pileio.page) at the University of Southampton:

Position #1: Post-Doctoral Research Fellowship in nuclear magnetic resonance in the research group of Dr Giuseppe Pileio, in collaboration with Prof Malcolm H Levitt. The project, funded by EPSRC(UK), concerns the development of hardware and methodology that combines supercritical fluids with long-lived states NMR and dissolution-DNP to prolong the storage of hyperpolarised spin order and allow it to be transported remotely from the production site. The successful candidate will be mainly responsible of the hardware development side of the project and will work together with a PhD student and another Research Fellow, both already appointed. Furthermore, the project is done in partnership with Jasco, a UK based company specialising in supercritical-fluids. The position is tenable from 13 Feb 2017 (or as soon as possible thereafter) with initial appointment for 2 years and there are already enough funds for a further extension of 1 year or more, subject to project requirement!

For further details and how to apply please follow this link: https://jobs.soton.ac.uk/Vacancy.aspx?ref=785816EB-R


Position #2: Post-Doctoral Research Fellowship in nuclear magnetic resonance in the research group of Dr Giuseppe Pileio. The project, funded by EPSRC, concerns the development of NMR methodology to probe translational dynamics in porous media by singlet-state NMR spectroscopy. In particular we are interested in developing new methods for measuring tortuosity in porous media and singlet-state enhanced q-space spectroscopy. The successful candidate will work together with a Project Student and another Research Fellow, both already working on the project. The position is tenable from 13 Feb 2017 (or as soon as possible thereafter) with appointment for 1 year but with the possibility of a further extension of 1 more year, subject to project requirements and mutual interests. For further details and how to apply please follow this link: https://jobs.soton.ac.uk/Vacancy.aspx?ref=785516EB-R

The closing date for both positions is 19 January 2017.

University of Southampton is a UK Russell Group university positioned in the top 1% of world universities according to QS World University Rankings. We have an international reputation for research, teaching and enterprise activities. Southampton is particularly well known for its magnetic resonance and computational chemistry research.


All the best,
Dr. Giuseppe Pileio, PhD

Lecturer in Magnetic Resonance,
Department of Chemistry,
Building 30 - Room 3047,
University of Southampton,
University Road, SO17 1BJ,
Internal Post Code: M16,
Southampton, Hampshire, UK.


Tel.: +44 (023) 80 59 4146<tel:+44%20(023)%2080%2059%204146>

====================================
This is the AMPERE MAGNETIC RESONANCE mailing list:

NMR web database:

Wednesday, January 4, 2017

Expeditious dissolution dynamic nuclear polarization without glassing agents


Lama, B., et al., Expeditious dissolution dynamic nuclear polarization without glassing agents. NMR Biomed, 2016. 29(3): p. 226-31.


The hyperpolarization of metabolic substrates at low temperature using dynamic nuclear polarization (DNP), followed by rapid dissolution and injection into an MRSI or NMR system, allows in vitro or in vivo observation and tracking of biochemical reactions and metabolites in real time. This article describes an elegant approach to sample preparation which is broadly applicable for the rapid polarization of aqueous small-molecule substrate solutions and obviates the need for glassing agents. We demonstrate its utility for solutions of sodium acetate, pyruvate and butyrate. The polarization behavior of substrates prepared using rapid freezing without glassing agents enabled a 1.5-3-fold time savings in polarization buildup, whilst removing the need for toxic glassing agents used as standard for dissolution DNP. The achievable polarization with fully aqueous substrate solutions was equal to that observed using standard approaches and glassing agents. Copyright (c) 2016 John Wiley & Sons, Ltd.

Monday, January 2, 2017

Antioxidant treatment attenuates lactate production in diabetic nephropathy


Laustsen, C., et al., Antioxidant treatment attenuates lactate production in diabetic nephropathy. American Journal of Physiology - Renal Physiology, 2016: p. ajprenal.00148.2016.


The early progression of diabetic nephropathy is notoriously difficult to detect and quantify prior to the occurrence of substantial histological damage. Recently, hyperpolarized [1-13C] pyruvate has demonstrated increased lactate production in the kidney early after the onset of diabetes, implying increased lactate dehydrogenase activity as a consequence of increased nicotinamide adenine dinucleotide substrate availability due to upregulation of the polyol pathway, i.e., pseudohypoxia. In this study, we investigated the role of oxidative stress in mediating these metabolic alterations using state-of-the-art hyperpolarized magnetic resonance (MR) imaging. Ten-week-old female Wistar rats were randomly divided into three groups: healthy controls, untreated diabetic (streptozotocin treatment to induce insulinopenic diabetes), and diabetic, receiving chronic antioxidant treatment with TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl) via the drinking water. Examinations were performed 2, 3, and 4 weeks after the induction of diabetes by using a 3T Clinical MR system equipped with a dual tuned 13C/1H-volume rat coil. The rats received intravenous hyperpolarized [1-13C] pyruvate and were imaged using a slice-selective 13C-IDEAL spiral sequence. Untreated diabetic rats showed increased renal lactate production compared to that shown by the controls. However, chronic TEMPOL treatment significantly attenuated diabetes-induced lactate production. No significant effects of diabetes or TEMPOL were observed on 13C-alanine levels, indicating an intact glucose-alanine cycle, or 13C-bicarbonate, indicating normal flux through the Krebs cycle. In conclusion, this study demonstrates that diabetes-induced pseudohypoxia, as indicated by an increased lactate-to-pyruvate ratio, is significantly attenuated by antioxidant treatment. This demonstrates a pivotal role of oxidative stress for renal metabolic alterations occurring in early diabetes.