Merging transcriptomics and metabolomics - advances in breast cancer profiling

Background Combining gene expression microarrays and high resolution magic angle spinning magnetic resonance spectroscopy (HR MAS MRS) of the same tissue samples enables comparison of the transcriptional and metabolic profiles of breast cancer. The aim of this study was to explore the potential of combining these two different types of information. Methods Breast cancer tissue from 46 patients was analyzed by HR MAS MRS followed by gene expression microarrays. Two strategies were used to combine the gene expression and metabolic data; first using multivariate analyses to identify different groups based on gene expression and metabolic data; second correlating levels of specific metabolites to transcripts to suggest new hypotheses of connections between metabolite levels and the underlying biological processes. A parallel study was designed to address experimental issues of combining microarrays and HR MAS MRS. Results In the first strategy, using the microarray data and previously reported molecular classification methods, the majority of samples were classified as luminal A. Three subgroups of luminal A tumors were identified based on hierarchical clustering of the HR MAS MR spectra. The samples in one of the subgroups, designated A2, showed significantly lower glucose and higher alanine levels than the other luminal A samples, suggesting a higher glycolytic activity in these tumors. This group was also enriched for genes annotated with Gene Ontology (GO) terms related to cell cycle and DNA repair. In the second strategy, the correlations between concentrations of myo-inositol, glycine, taurine, glycerophosphocholine, phosphocholine, choline and creatine and all transcripts in the filtered microarray data were investigated. GO-terms related to the extracellular matrix were enriched among the genes that correlated the most to myo-inositol and taurine, while cell cycle related GO-terms were enriched for the genes that correlated the most to choline. Additionally, a subset of transcripts was identified to have slightly altered expression after HR MAS MRS and was therefore removed from all other analyses. Conclusions Combining transcriptional and metabolic data from the same breast carcinoma sample is feasible and may contribute to a more refined subclassification of breast cancers as well as reveal relations between metabolic and transcriptional levels. See Commentary: http://www.biomedcentral.com/1741-7015/8/7

Electron paramagnetic resonance applications: from drug discovery to marine biology studies

El leitmotiv de la tesis es el uso de la técnica EPR, que implica el estudio de la dinámica de interacción de sistemas de interés con la ayuda de especies paramagnéticas apropiadas. El trabajo realizado en los tres años del doctorado se centró en el estudio químico-físico de moléculas de uso biomédico, más un trabajo extra sobre la interacción químico-física entre algunas formas de fitoplancton y microplásticos. La tesis se desarrolla en tres líneas de investigación: 1. El estudio de los glicodendrímeros para el tratamiento de la enfermedad de Wilson ocupó la mayor parte del primer año. Una nueva familia de glicodendrímeros, modificados con grupos DOTA, fue sintetizada el centro de investigación Leibniz-Intitute de Dresden, y analizada para evaluar su habilidad de quelar átomos de Cu(II). En particular, se puso bajo la lupa la interacción químico-física entre estas moléculas y los modelos de membrana, que confirmó su posible aplicación en campo biomédico. Este estudio condujo a la redacción de un artículo publicado en Langmuir. 2. Durante los tres años, se trabajó en la síntesis, caracterización y aplicación de metalodendrímeros para el tratamiento de diversas formas de neoplasia. La combinación de esta clase de polímeros e iones metálicos permite un control fino de los mecanismos anticancerígenos, que pueden moldearse según el sistema en estudio. Nuevas familias de metalodendrímeros de cobre y rutenio fueron sintetizadas en Alcalá y estudiadas bajo un punto de vista químico-físico en la universidad de Urbino. En este contexto, se han publicado 3 artículos y una reseña, además de un último artículo en proceso de peer review. 3. Un proyecto nacido y concluido en pocos meses con la publicación de un artículo en Chemosphere, se refiere a la demostración de la interacción física de algunos tipos de fitoplancton y microplásticos presentes en el Mediterráneo, para explicar un fenómeno particular de bio-contaminación que ha surgido en los últimos años. Dicha interacción fue estudiada en Urbino por medio de técnicas químico-físicas

Magnetic Resonance Characterization of Porous Media Using Diffusion through Internal Magnetic Fields

When a porous material is inserted into a uniform magnetic field, spatially varying fields typically arise inside the pore space due to susceptibility contrast between the solid matrix and the surrounding fluid. As a result, direct measurement of the field variation may provide a unique opportunity to characterize the pore geometry. The sensitivity of nuclear magnetic resonance (NMR) to inhomogeneous field variations through their dephasing effects on diffusing spins is unique and powerful. Recent theoretical and experimental research sheds new light on how to utilize susceptibility-induced internal field gradients to quantitatively probe the microstructure of porous materials. This article reviews ongoing developments based on the stimulated echo-pulse sequence to extend the characterization of porous media using both spatially resolved and unresolved susceptibility-induced internal gradients that operate on a diffusing-spin ensemble.open

Developing novel diffusion MRI methods for comprehensive analysis of restricted and anisotropic self-diffusion system

Diffusion MRI is a non-invasive imaging technique used to study the microstructural properties of biological tissues by observing the self-diffusion of water molecules. Traditional diffusion MRI methods, based on the pulsed gradient spin-echo sequence, employ magnetic field gradients to encode information about translational motion. However, this approach combines various aspects of diffusion, such as restriction, anisotropy, and flow, into a single observable, leading to interpretation ambiguities, especially in complex heterogeneous materials like living biological tissues.In this thesis, we address these challenges and push the boundaries of diffusion MRI by introducing innovative techniques for studying biological tissue microstructure. Our approach centers around the "double-rotation" technique borrowed from solid-state NMR, which generates modulated gradient waveforms, enabling us to explore the 2D frequency-anisotropy domain in-depth. By integrating this technique with oscillating gradients and tensor-valued encoding, we create a comprehensive methodology for data acquisition. Drawing inspiration from the "model-free" analytical strategies originally designed for studying rotational dynamics in macromolecules, we extend its applicability to MRI techniques for understanding diffusion in biological tissues.Through a series of proof-of-principle experiments, we validate our novel acquisition and analysis strategy across various samples. These experiments encompass the study of isotropic and anisotropic Gaussian diffusion in simple liquids, characterizing anisotropic Gaussian diffusion in a lyotropic liquid crystal with lamellar microstructure, and exploring restricted diffusion in a yeast cell sediment. Additionally, we showcase the effectiveness of our methods on ex vivo mouse brain and tumor tissue, highlighting the practical potential of our approach.Our proposed double-rotation gradient waveforms enable comprehensive sampling of both the frequency and "shape" dimensions of diffusion encoding, providing detailed insights into restriction and anisotropy in heterogeneous materials. The implications of our work extend to model-free investigations, allowing us to understand microstructural changes linked with pathology or normal brain development

59th Annual Rocky Mountain Conference on Magnetic Resonance

Final program, abstracts, and information about the 59th annual meeting of the Rocky Mountain Conference on Magnetic Resonance, co-endorsed by the Colorado Section of the American Chemical Society and the Society for Applied Spectroscopy. Held in Snowbird, Utah, July 22-27, 2018

56th Annual Rocky Mountain Conference on Magnetic Resonance

Final program, abstracts, and information about the 56th annual meeting of the Rocky Mountain Conference on Magnetic Resonance, co-endorsed by the Colorado Section of the American Chemical Society and the Society for Applied Spectroscopy. Held in Copper Mountain, Colorado, July 13-17, 2014

53rd Rocky Mountain Conference on Analytical Chemistry

Final program, abstracts, and information about the 53rd annual meeting of the Rocky Mountain Conference on Analytical Chemistry, co-endorsed by the Colorado Section of the American Chemical Society and the Society for Applied Spectroscopy. Held in Snowmass, Colorado, July 24-28, 2011

The Integration of Positron Emission Tomography With Magnetic Resonance Imaging

A number of laboratories and companies are currently exploring the development of integrated imaging systems for magnetic resonance imaging (MRI) and positron emission tomography (PET). Scanners for both preclinical and human research applications are being pursued. In contrast to the widely distributed and now quite mature PET/computed tomography technology, most PET/MRI designs allow for simultaneous rather than sequential acquisition of PET and MRI data. While this offers the possibility of novel imaging strategies, it also creates considerable challenges for acquiring artifact-free images from both modalities. This paper discusses the motivation for developing combined PET/MRI technology, outlines the obstacles in realizing such an integrated instrument, and presents recent progress in the development of both the instrumentation and of novel imaging agents for combined PET/MRI studies. The performance of the first-generation PET/MRI systems is described. Finally, a range of possible biomedical applications for PET/MRI are outlined

Tinkering with the Unbearable Lightness of Being: Meditation, Mind-Body Medicine and Placebo in the Quantum Biology Age

There are empirical indications that mind-body therapies have a nonlocal quantum component, in addition to the psychoneuroimmunological pathways that have been the focus of the predominant experimental paradigm.  The discussion below addresses the evidence and proposed theoretical mechanisms supporting this conclusion, and makes the case that there should be a convergence of research agendas between mind-body interventions (including placebo),  photomedicine and quantum biology.  Specifically, the role of endogenously generated biophotons in the regulation of genetic expression and the apparent ability of mental intent to direct biophoton emissions to specifically targeted tissues needs to be further evaluated from the perspective of photobiomodulation mechanisms, with a special focus on the spectroscopy and dosimetry of these emissions. Finally, the possible role of long-term meditation in enhancing quantum biological effects has to be further investigated at the level of cellular and macromolecular remodeling, both in the brain and the body