Data_Sheet_1_A Comparative Study of Diffusion Fiber Reconstruction Models for Pyramidal Tract Branches.docx

Currently, comparative studies evaluating the quantification accuracy of pyramidal tracts (PT) and PT branches that were tracked based on four mainstream diffusion models are deficient. The present study aims to evaluate four mainstream models using the high-quality Human Connectome Project (HCP) dataset. Diffusion tensor imaging (DTI), diffusion spectral imaging (DSI), generalized Q-space sampling imaging (GQI), and Q-ball imaging (QBI) were used to construct the PT and PT branches in 50 healthy volunteers from the HCP. False and true PT fibers were identified based on anatomic information. One-way repeated measure analysis of variance and post hoc paired-sample t-test were performed to identify the best PT and PT branch quantification model. The number, percentage, and density of true fibers of PT obtained based on GQI and QBI were significantly larger than those based on DTI and DSI (all p trunk) were present in the four diffusion models compared with the upper limb (PTUlimb), lower limb (PTLlimb), and cranial (PTcranial) branches. In addition, significantly more true fibers were obtained in PTtrunk, PTUlimb, and PTLlimb based on the GQI and QBI compared with DTI and DSI (all p < 0.0005, Bonferroni corrected). Finally, GQI-based group probabilistic maps showed that the four PT branches exhibited relatively unique spatial distributions. Therefore, the GQI and QBI represent better diffusion models for the PT and PT branches. The group probabilistic maps of PT branches have been shared with the public to facilitate more precise studies on the plasticity of and the damage to the motor pathway.</p

Metabolic Perturbance in Autism Spectrum Disorders: A Metabolomics Study

Autism spectrum disorders (ASD) are a group of biological disorders with associated metabolic derangement. This study aimed to identify a pattern of metabolic perturbance in ASD using metabolomics in urinary specimens from 48 children with ASD and 53 age matched controls. Using a combination of liquid- and gas-chromatography-based mass spectrometry, we detected the levels of 82 metabolites (53 of which were increased) that were significantly altered between the ASD and the control groups using osmolality normalized data. Pattern analysis showed that the levels of several amino acids such as glycine, serine, threonine, alanine, histidine, glutamyl amino acids and the organic acid, taurine were significantly (<i>p</i> ≤ 0.05) lower in ASD children. The levels of antioxidants such as carnosine were also reduced in ASD (<i>p</i> = 0.054). Furthermore, several gut bacterial metabolites were significantly altered in ASD children who had gastrointestinal dysfunction. Overall, this study detected abnormal amino acid metabolism, increased oxidative stress, and altered gut microbiomes in ASD. The relationship of altered gut microbial co-metabolism and the disrupted metabolisms requires further investigation

Inflammation and Resolution Are Associated with Upregulation of Fatty Acid β-Oxidation in Zymosan-Induced Peritonitis

<div><p>Inflammation is a fundamental defensive response to harmful stimuli. However, it can cause damage if it does not subside. To avoid such damage, organisms have developed a mechanism called resolution of inflammation. Here we applied an untargeted metabolomics approach to a sterile and self-resolving animal model of acute inflammation, namely zymosan-induced peritonitis in mice, to examine the effect of inflammation and resolution on the metabolomic profiles. Significant and time-dependent changes in metabolite profiles after zymosan administration were observed in both peritoneal wash fluid (PWF) and plasma. These metabolomic changes correlated well with inflammatory chemokine or cytokine production. In PWF, most of metabolites that could detected increased in zymosan-treated mice, which is suggestive of inflammation, oxidative stress and increased energy demands. In plasma, most metabolites in the central metabolic pathway (glycolysis and TCA cycle) were significantly downregulated after zymosan administration. The concentration of the ketone body 3-hydroxybutyric acid (3-HB) in plasma and PWF increased in zymosan-injected animals indicating upregulation of fatty acid β-oxidation. Increased 3-HB level was observed in the cells that infiltrated into the peritoneal cavity and these infiltrated cells might contribute, at least in part, to the production of 3-HB in the peritoneal cavity.</p></div

Relative concentration time courses of 3-hydroxybutyric acid in PWF (A) and plasma (B) after an intraperitoneal administration of zymosan or vehicle control in mice.

<p>These metabolites levels are expressed as mean±s.e.m (n = 5). *<i>P</i><0.05, **<i>P</i><0.01, compared with vehicle control.</p

Table 3. Concentrations of 3-HB in the cells that infiltrated into the peritoneal cavity, PWF, and plasma in control and zymosan-treated (10 mg) animals.

<p>Concentrations are expressed as mean ± s.e.m (n = 5). The asterisks indicate significant differences (** <i>P</i><.01 and * <i>P</i><.05) compared to the vehicle control. Since the 3-HB concentrations of PWF in vehicle control animals were not detectable (ND, detection limit; 0.001 mM), statistical analysis could not be performed.</p

Time course of principle component analysis (PCA) score plot of PWF metabolomics data.

<p>Black symbols: control animals, blue: zymosan 1 mg administered animals, red: zymosan 10 mg administered animals, respectively. Black eclipse in the score plot illustrates the 95% confidence regions.</p

Correlation plots comparing BBB scores with metabolite levels at days 11 (circle) and 30 (square).

<p>The eight named metabolites with the highest |R| score are displayed (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0043152#pone.0043152.s002" target="_blank">Table S2</a> for complete list). Sham animals (day 11 and 30) received full BBB score ( = 21), consistent with normal movement. SCI at day 11 and 30 are depicted as •(n = 7) and ▪(n = 8). Sham at day 11 and 30 are displayed as ○(n = 8) and □(n = 8). All data points of Sham animals and SCI animals were used to calculate the R values.</p

Concentration time courses of IL-1β, TNF-α, IFN-γ and MIP-1α in peritoneal wash fluid (PWF) after an intraperitoneal administration of zymosan or vehicle control in mice.

<p>Cytokine and chemokine levels are expressed as mean±s.e.m. (n = 5). LLOQ means lower limit of quantification.</p

Correlation between absolute NAA concentration in the spinal cord and the corresponding BBB scores 32–34 days after SCI.

<p>SCI was induced by 100, 150 or 200-kdyn impact force. Sham animals received full BBB score ( = 21), consistent with normal movement.</p

Metabolite Profiles Correlate Closely with Neurobehavioral Function in Experimental Spinal Cord Injury in Rats

<div><p>Traumatic spinal cord injury (SCI) results in direct physical damage and the generation of local factors contributing to secondary pathogenesis. Untargeted metabolomic profiling was used to uncover metabolic changes and to identify relationships between metabolites and neurobehavioral functions in the spinal cord after injury in rats. In the early metabolic phase, neuronal signaling, stress, and inflammation-associated metabolites were strongly altered. A dynamic inflammatory response consisting of elevated levels of prostaglandin E2 and palmitoyl ethanolamide as well as pro- and anti-inflammatory polyunsaturated fatty acids was observed. <em>N-</em>acetyl-aspartyl-glutamate (NAAG) and <em>N-</em>acetyl-aspartate (NAA) were significantly decreased possibly reflecting neuronal cell death. A second metabolic phase was also seen, consistent with membrane remodeling and antioxidant defense response. These metabolomic changes were consistent with the pathology and progression of SCI. Several metabolites, including NAA, NAAG, and the ω-3 fatty acids docosapentaenoate and docosahexaenoate correlated greatly with the established Basso, Beattie and Bresnahan locomotive score (BBB score). Our findings suggest the possibility of a biochemical basis for BBB score and illustrate that metabolites may correlate with neurobehavior. In particular the NAA level in the spinal cord might provide a meaningful biomarker that could help to determine the degree of injury severity and prognosticate neurologic recovery.</p> </div