HP ¹²⁹Xe spectrum obtained from rat brain <i>in vivo</i> after the administration of HP ¹²⁹Xe gas.

<p>The spectrum was acquired from 50 averages using an RF pulse with a flip angle of 90°, and a frequency of 55.477 MHz. At least four separate peaks are discernable, the largest of which occurs at 194.7 ppm downfield from the HP ¹²⁹Xe gas peak at 0 ppm. The SNR of the largest peak is 476.</p

HP ¹²⁹Xe distribution in the rat brain.

<p>(<b>3a</b>) HP ¹²⁹Xe CSI image acquired with a 2D CSI pulse sequence from rat head under normal breathing conditions (slice thickness 10 mm). (<b>3b</b>) same image with false color applied. Warmer colors indicate increased HP ¹²⁹Xe signal intensity. (<b>3c</b>) Proton MRI of a rat head showing a 1 mm coronal slice through the brain acquired with a RARE pulse sequence. (<b>3d</b>) Proton image shown with overlay of HP ¹²⁹Xe MRI, in which only HP ¹²⁹Xe signal with an SNR above 2 are shown. FOV was 25 mm.</p

Superimposition of a rat brain atlas [<b>18</b>] showing four regions of interest (ROIs) analyzed for changes in HP ¹²⁹Xe signal following forepaw stimulation, including cingulate cortex (Cg), primary somatosensory cortex and SS1 forelimb region (SS1 and SS1 fl), and secondary samatosensory cortex (SS2).

<p>Superimposition of a rat brain atlas <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0021607#pone.0021607-Paxinos1" target="_blank">[<b>18</b>]</a> showing four regions of interest (ROIs) analyzed for changes in HP ¹²⁹Xe signal following forepaw stimulation, including cingulate cortex (Cg), primary somatosensory cortex and SS1 forelimb region (SS1 and SS1 fl), and secondary samatosensory cortex (SS2).</p

Vital Signs Data (N = 3).

<p>Vital Signs Data (N = 3).</p

RF coil used for image acquisition.

<p>The dual frequency coil combines a Helmholtz pair proton coil (transmit and receive, 200 MHz) nested on a single loop ¹²⁹Xe coil (transmit and receive, 55.35 MHz). This coil architecture allowed proton and ¹²⁹Xe images to be acquired sequentially while maintaining exact co-registration (Clinical MR Solutions, Brookfield, WI). The two coils were intrinsically decoupled.</p

HP ¹²⁹Xe fMRI data from three animals.

<p>The HP ¹²⁹Xe signal is shown as a false colour overlay on the corresponding 1 mm thick coronal proton reference image taken from the same animal. The left panel shows HP ¹²⁹Xe signal intensity during baseline and the right panel shows HP ¹²⁹Xe signal intensity after injection of capsaicin 20 ul (3 mg/ml) into the right forepaw. Colour scale represents SNR and only signal with SNR above 2 are shown. Superimposition of a rat brain atlas (18) demarcates specific areas of the brain: cingulate cortex (Cg), motor cortex (M), primary somatosensory cortex and SS1 forelimb region (SS1 and SS1 fl), secondary samatosensory cortex (SS2), and striatum (CPu).</p

Percent HP ¹²⁹Xe signal change in four brain regions^*.

<p>*Measured from regions of interest (ROIs) in hemisphere contralateral to pain stimulus.</p

DataSheet_1_Transcriptome-wide association study of circulating IgE levels identifies novel targets for asthma and allergic diseases.docx

Measurement of circulating immunoglobulin E (IgE) concentration is helpful for diagnosing and treating asthma and allergic diseases. Identifying gene expression signatures associated with IgE might elucidate novel pathways for IgE regulation. To this end, we performed a discovery transcriptome-wide association study to identify differentially expressed genes associated with circulating IgE levels in whole-blood derived RNA from 5,345 participants in the Framingham Heart Study across 17,873 mRNA gene-level transcripts. We identified 216 significant transcripts at a false discovery rate <0.05. We conducted replication using the meta-analysis of two independent external studies: the Childhood Asthma Management Program (n=610) and the Genetic Epidemiology of Asthma in Costa Rica Study (n=326); we then reversed the discovery and replication cohorts, which revealed 59 significant genes that replicated in both directions. Gene ontology analysis revealed that many of these genes were implicated in immune function pathways, including defense response, inflammatory response, and cytokine production. Mendelian randomization (MR) analysis revealed four genes (CLC, CCDC21, S100A13, and GCNT1) as putatively causal (p<0.05) regulators of IgE levels. GCNT1 (beta=1.5, p=0.01)—which is a top result in the MR analysis of expression in relation to asthma and allergic diseases—plays a role in regulating T helper type 1 cell homing, lymphocyte trafficking, and B cell differentiation. Our findings build upon prior knowledge of IgE regulation and provide a deeper understanding of underlying molecular mechanisms. The IgE-associated genes that we identified—particularly those implicated in MR analysis—can be explored as promising therapeutic targets for asthma and IgE-related diseases.</p