These are short reports about the research activities carried out at the SeRMN.
In them we describe the work done in collaboration with research groups, to summarize communications presented at scientific meetings, to report visits and stages at other laboratories or facilities, and to comment the meetings and workshops we have attended.
Nolis, Pau, Kumar Motiram-Corral, Míriam Pérez-Trujillo & Teodor Parella. 2019. Simultaneous acquisition of two 2D HSQC spectra with different 13C spectral widths. Journal of Magnetic Resonance. DOI: 10.1016/j.jmr.2019.01.004
ABSTRACT: A time-efficient NMR strategy that involves the interleaved acquisition of two 2D HSQC spectra having different spectral widths in the indirect 13C dimension is presented. We show how the two equivalent coherence transfer pathways involved in sensitivity-enhanced HSQC experiments are managed selectively and detected separately in different FID periods within the same scan. The feasibility of this new SADA-HSQC (Spectral Aliasing in Dually Acquired HSQC) technique is demonstrated by recording simultaneously two complementary datasets, conventional and highly-resolved spectral-aliased 2D HSQC spectra, in a single NMR experiment. Combining the information from both datasets, accurate chemical shift determination and excellent signal dispersion is achieved in a unique measurement using only few t1 increments.
Simões, Rui V., Miquel E. Cabañas, Carla Loreiro, Miriam Illa, Fatima Crispi & Eduard Gratacós. 2018. Assessment of prenatal cerebral and cardiac metabolic changes in a rabbit model of fetal growth restriction based on 13C-labelled substrate infusions and ex vivo multinuclear HRMAS. PLOS ONE 13(12). e0208784. DOI: 10.1371/journal.pone.0208784
Background: We have used a previously reported rabbit model of fetal growth restriction (FGR), reproducing perinatal neurodevelopmental and cardiovascular impairments, to investigate the main relative changes in cerebral and cardiac metabolism of term FGR fetuses during nutrient infusion.
Methods: FGR was induced in 9 pregnant New Zealand rabbits at 25 days of gestation: one horn used as FGR, by partial ligation of uteroplacental vessels, and the contralateral as control (appropriate for gestation age, AGA). At 30 days of gestation, fasted mothers under anesthesia were infused i.v. with 1-13C-glucose (4 mothers), 2-13C-acetate (3 mothers), or not infused (2 mothers). Fetal brain and heart samples were quickly harvested and frozen down. Brain cortex and heart apex regions from 30 fetuses were studied ex vivo by HRMAS at 4°C, acquiring multinuclear 1D and 2D spectra. The data were processed, quantified by peak deconvolution or integration, and normalized to sample weight.
We are recruiting an Early Stage Researcher to work on the implementation of high-resolution MRSI methods in a pre-clinical scanner as part of the INSPiRE-MED European project.
We seek a highly motivated and qualified individual as Early Stage Researcher for a three-year applied research project. The successful candidate will contribute to the development of advanced biomedical research tools in the field of Magnetic Resonance Spectroscopy and Imaging, and its application to the clinical day-to-day practice.
Project description: This position is one of the 15 ESR positions of the INSPiRE-MED European Training Network, which focuses on the development of Magnetic Resonance Spectroscopy (MRS) and MR Spectroscopic Imaging (MRSI) combined with Positron Emission Tomography (PET), enhanced by machine learning techniques.
The main aim of the PhD project (ESR4) will be the implementation of innovative high spatial resolution MRSI methods in a pre-clinical scanner. The ultimate goal will be the validation of optimal methods for improving imaging biomarker development of brain tumour in longitudinal studies of therapy response in mouse glioblastoma models. The project will involve evaluation of the methodology performance limits, repeatability and reproducibility compared to stock Bruker Biospec MRSI sequences and the assessment of speed-up MRSI methods in a 7-Tesla pre-clinical scanner.
Integrating Magnetic Resonance Spectroscopy and Multimodal Imaging for Research and Education in MEDicine (INSPiRE-MED) is an European research project awarded in the call H2020-MSCA-ITN-2018, of the MSCA-ITN-ETN – European Training Networks, to a consortium of partners including the GABRMN and SeRMN at UAB. The project is coordinated by Prof. Dominique Sappey-Marinier, of the Université Lyon-1 Claude-Bernard, Lyon, France. The scientist-in-charge at UAB will be Prof. Carles Arús (GABRMN), and Silvia Lope-Piedrafita (SeRMN) and Miquel Cabañas (SeRMN) will participate as senior scientists in the project.
Starting 1st of January 2019, the INSPiRE-MED Initial Training Network will investigate the theoretical and practical aspects of in vivo Magnetic Resonance Spectroscopy (MRS) and Spectroscopic Imaging (MRSI) with applications in oncology and neurology.
The network will host 15 Early Stage Researchers in the field of biomedical imaging, particularly in the field of Magnetic Resonance Spectroscopy (MRS) and MR Spectroscopic Imaging (MRSI) combined with Positron Emission Tomography (PET) and enhanced by machine learning techniques. The research training is supervised by a consortium of 12 academic partners with an established collaborative track record in R&D and 9 industrial partners from the broad and competitive preclinical and clinical imaging sector.
The main research topic to be carried at UAB —in close collaboration with other project members— will be the implementation of innovative high spatial resolution MRSI methods in a pre-clinical scanner. The ultimate goal will be the validation of optimal methods for improving imaging biomarker development of brain tumour in longitudinal studies of therapy response in mouse glioblastoma models.
Nolis, Pau, Kumar Motiram‐Corral, Míriam Pérez‐Trujillo & Teodor Parella. 2018. Interleaved Dual NMR Acquisition of Equivalent Transfer Pathways in TOCSY and HSQC Experiments. ChemPhysChem 20(3). 356–360. DOI: 10.1002/cphc.201801034
A dual NMR data acquisition strategy to handle and detect two active equivalent transfer pathways is presented and discussed. We illustrate the power of this time-efficient approach by collecting two different 2D spectra simultaneously in a single experiment: (i) TOCSY or HSQC-TOCSY spectra with different mixing times, (ii) F2-13C-coupled and decoupled HSQC spectra, (iii) conventional and pureshift HSQC spectra, and (iv) complementary HSQC and HSQC-TOCSY spectra.
Nolis, Pau, Kumar Motiram-Corral, Míriam Pérez-Trujillo & Teodor Parella. 2019. Broadband homodecoupled time-shared 1H-13C and 1H-15N HSQC experiments. Journal of Magnetic Resonance 298. 23–30. DOI: 10.1016/j.jmr.2018.11.00
The concepts of pure-shift NMR and time-shared NMR are merged in a single NMR experiment. A 13C/15N time-shared version of the real-time BIRD-based broadband homodecoupled HSQC experiment is described. This time-efficient approach affords simultaneously 1H-13C and 1H-15N pure-shift HSQC spectra in a single acquisition, while achieving substantial gains in both sensitivity and spectral resolution. We also present a related 13C/15N-F2-coupled homodecoupled version of the CLIP-HSQC experiment for the simultaneous measurement of 1JCH and 1JNH from the simplified doublets observed along the direct dimension. Finally, a novel J-resolved HSQC experiment has been designed for the simple and automated determination of both 1JCH/1JNH from a 2D J-resolved spectrum.
Motiram-Corral, Kumar, Míriam Pérez-Trujillo, Pau Nolis & Teodor Parella. 2018. Implementing one-shot multiple-FID acquisition into homonuclear and heteronuclear NMR experiments. Chemical Communications 54(96). 13507–13510. DOI: 10.1039/c8cc08065h
Multiple-FID acquisition (MFA) within the same scan is applied to acquire simultaneously multiple 2D spectra from a single NMR experiment. A discussion on the incorporation of the MFA strategy in several homonuclear and heteronuclear 2D pulse sequences is presented. As a proof of concept, a set of novel COSY, TOCSY and HMBC experiments are reported as a time-efficient solution in small-molecule NMR spectroscopy.
This study aims to explore the biological functions of the isolated exopolysaccharides (EPSs) produced during the industrial fermentation of olives against enterotoxigenic E. coli (ETEC) K88. Exopolysaccharides were isolated from five industrial fermenters. Analysis of their monosaccharide composition by GLC revealed that the main components were glucose (27%–50%) and galactose (23%–33%) followed by rhamnose (4–23%) and arabinose (6–17%). The 1H NMR spectrum showed a very similar profile between samples, and a more in-depth analysis revealed the presence of an α-pyranose in the form of α-D-Glcp-(1→) and two different α-furanoses, with chemicals shift values, suggesting the presence of α-D-Glcf and α-D-Galf. Miniaturized in vitro tests demonstrated the ability of EPS samples to attach specifically to ETEC K88 (P < 0.05) with variable intensities. The competition test did not show the ability to block the ETEC K88 adhesion to IPEC-J2 cells; however, in the displacement test, all EPS samples were shown to effectively remove the pathogens attached to the cells (P < 0.01).
These results suggest that the EPSs produced during the fermentation of table green olives could interfere with the attachment of opportunistic pathogens onto the intestinal epithelial cells. This would open the possibility of novel functional properties for this traditional Mediterranean fermented food and for the isolated EPSs as candidates for nutraceutics to be used in human and/or animal diets in the prevention and treatment of ETEC diarrhoea.
The present doctoral thesis is framed within the field of Nuclear Magnetic Resonance (NMR) spectroscopy.
NMR spectroscopy is an analytic technique and, therefore, one of its main objectives is to unravel the correct structure of the molecules analyzed.This present doctoral thesis is focused on this main objective. This work consists in a compendium of 7 publications, written in several prestigious scientific journals, that develop in depth the efficient and accurate determination of the constitution, configuration and conformation of small molecules thanks to the application of resolution improvements techniques.
On 21st March 2018 I sucessfully defended my PhD Thesis entitled: “New Applications of Covariance NMR and Experimental Development for Measurements of Homonuclear Coupling Constants in Overlapping Signals” (ISBN: 9788449079252), supervised by Dr. Teodor Parella and Dr. Pau Nolis, and obtained the degree of Ph.D. in Chemistry at the Department of Chemistry, Universitat Autònoma de Barcelona.
The experimental results obtained in this thesis are presented in the form of three papers published in NMR specialised scientific peer-reviewed journals.
Exploring the use of Generalized Indirect Covariance to Reconstruct Pure shift NMR Spectra: Current Pros and Cons. André Fredi, Pau Nolis, Carlos Cobas, Gary E. Martin and Teodor Parella. Journal of Magnetic Resonance, Volume 266, May 2016, Pages 16-22. DOI: 10.1016/j.jmr.2016.03.003
Access to experimentally infeasible spectra by pure-shift NMR covariance. André Fredi, Pau Nolis, Carlos Cobas and Teodor Parella. Journal of Magnetic Resonance, Volume 270, September 2016, Pages 161-168. DOI: 10.1016/j.jmr.2016.07.010
Accurate measurement of JHH in overlapped signals by a TOCSY‐edited SERF Experiment. André Fredi, Pau Nolis and Teodor Parella. Magnetic Resonance in Chemistry, Volume 55, Issue 6, June 2017, Pages 525-529. DOI: 10.1002/mrc.4572
The first two articles deal with the use of covariance NMR as a general method to generate novel psNMR spectra. The last work describes a new selTOCSY G-SERF experiment, for accurately measuring JHH in overlapped regions.
The first publication describes a novel general protocol to generate psNMR spectra by Covariance NMR. This new approach is unique in NMR spectroscopy; giving a cheap, fast an easy way to reconstruct psNMR spectra without spending time in the spectrometer. This new strategy has been referenced to as psNMR Covariance.
The concept of psNMR Covariance has been extended in the second publication by inserting Multiplicity-Edited (ME) information into 2D experiments that are difficult or even impossible to achieve experimentally. It is shown how the ME information can be efficiently transferred to a set of homonuclear and heteronuclear 2D NMR spectra by Covariance processing, reconstructing new psME spectra in a fast way. Finally, G-SERF and related methods only work for isolated 1H signals on which selective excitation can be successfully applied.
Unfortunately, as it happens in other frequency-selective experiments, this approach fails for overlapped signals. A doubly-selective TOCSY G-SERF scheme is presented in the third publication to circumvent this limitation, by measuring JHH efficiently even for protons resonating in crowded regions.