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1.  Neuroanatomical Correlates of Intelligence in Healthy Young Adults: The Role of Basal Ganglia Volume 
PLoS ONE  2014;9(4):e93623.
In neuropsychiatric diseases with basal ganglia involvement, higher cognitive functions are often impaired. In this exploratory study, we examined healthy young adults to gain detailed insight into the relationship between basal ganglia volume and cognitive abilities under non-pathological conditions.
Methodology/Principal Findings
We investigated 137 healthy adults that were between the ages of 21 and 35 years with similar educational backgrounds. Magnetic resonance imaging (MRI) was performed, and volumes of basal ganglia nuclei in both hemispheres were calculated using FreeSurfer software. The cognitive assessment consisted of verbal, numeric and figural aspects of intelligence for either the fluid or the crystallised intelligence factor using the intelligence test Intelligenz-Struktur-Test (I-S-T 2000 R). Our data revealed significant correlations of the caudate nucleus and pallidum volumes with figural and numeric aspects of intelligence, but not with verbal intelligence. Interestingly, figural intelligence associations were dependent on sex and intelligence factor; in females, the pallidum volumes were correlated with crystallised figural intelligence (r = 0.372, p = 0.01), whereas in males, the caudate volumes were correlated with fluid figural intelligence (r = 0.507, p = 0.01). Numeric intelligence was correlated with right-lateralised caudate nucleus volumes for both females and males, but only for crystallised intelligence (r = 0.306, p = 0.04 and r = 0.459, p = 0.04, respectively). The associations were not mediated by prefrontal cortical subfield volumes when controlling with partial correlation analyses.
The findings of our exploratory analysis indicate that figural and numeric intelligence aspects, but not verbal aspects, are strongly associated with basal ganglia volumes. Unlike numeric intelligence, the type of figural intelligence appears to be related to distinct basal ganglia nuclei in a sex-specific manner. Subcortical brain structures thus may contribute substantially to cognitive performance.
PMCID: PMC3974758  PMID: 24699871
3.  Cardiac troponin I elevation with supraventricular tachycardia: two case reports and review of the literature 
BMC Research Notes  2014;7:136.
Although cardiac troponin I gives excellent accuracy in the identification of myocardial necrosis, it can also be elevated in a series of diseases other than acute coronary syndromes.
Case presentation
We present two cases of Chinese patients with a high serum troponin I level after an acute episode of paroxysmal supraventricular tachycardia with normal coronary arteries via angiography.
Abnormal troponin elevations can be seen in patients presenting with paroxysmal supraventricular tachycardia and angiographically-normal coronary arteries. Caution is advised with the use of invasive assessments such as coronary angiography in the differential diagnosis of patients with paroxysmal supraventricular tachycardia and elevated troponin levels.
PMCID: PMC3975268  PMID: 24618063
Cardiac troponin I; Acute coronary syndromes; Paroxysmal supraventricular tachycardia
4.  Effect of vitamin B12 on cleft palate induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin and dexamethasone in mice*  
The purpose of this study was to investigate the effect of vitamin B12 on palatal development by co-administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and dexamethasone (DEX). We examined the morphological and histological features of the palatal shelf and expression levels of key signaling molecules (transforming growth factor-β3 (TGF-β3) and TGF-β type I receptor (activin receptor-like kinase 5, ALK5)) during palatogenesis among a control group (Group A), TCDD+DEX exposed group (Group B), and TCDD+DEX+vitamin B12 exposed group (Group C). While we failed to find that vitamin B12 decreased the incidence of cleft palate induced by TCDD+DEX treatment, the expression levels of key signaling molecules (TGF-β3 and ALK5) during palatogenesis were significantly modulated. In TCDD+DEX exposed and TCDD+DEX+vitamin B12 exposed groups, palatal shelves could not contact in the midline due to their small sizes. Our results suggest that vitamin B12 may inhibit the expression of some cleft palate inducers such as TGF-β3 and ALK5 in DEX+TCDD exposed mice, which may be beneficial against palatogenesis to some degree, even though we were unable to observe a protective role of vitamin B12 in morphological and histological alterations of palatal shelves induced by DEX and TCDD.
PMCID: PMC3955916  PMID: 24599693
Cleft palate; Transforming growth factor-β3 (TGF-β3); Activin receptor-like kinase 5 (ALK5); Vitamin B12; 2,3,7,8-Tetrachlorodibenzo-p-dioxin; Dexamethasone
5.  Establishment of an inducing medium for type III effector secretion in Xanthomonas campestris pv. campestris 
Brazilian Journal of Microbiology  2014;44(3):945-952.
It is well known that the type III secretion system (T3SS) and type III (T3) effectors are essential for the pathogenicity of most bacterial phytopathogens and that the expression of T3SS and T3 effectors is suppressed in rich media but induced in minimal media and plants. To facilitate in-depth studies on T3SS and T3 effectors, it is crucial to establish a medium for T3 effector expression and secretion. Xanthomonas campestris pv. campestris (Xcc) is a model bacterium for studying plant-pathogen interactions. To date no medium for Xcc T3 effector secretion has been defined. Here, we compared four minimal media (MME, MMX, XVM2, and XOM2) which are reported for T3 expression induction in Xanthomonas spp. and found that MME is most efficient for expression and secretion of Xcc T3 effectors. By optimization of carbon and nitrogen sources and pH value based on MME, we established XCM1 medium, which is about 3 times stronger than MME for Xcc T3 effectors secretion. We further optimized the concentration of phosphate, calcium, and magnesium in XCM1 and found that XCM1 with a lower concentration of magnesium (renamed as XCM2) is about 10 times as efficient as XCM1 (meanwhile, about 30 times stronger than MME). Thus, we established an inducing medium XCM2 which is preferred for T3 effector secretion in Xcc.
PMCID: PMC3910216  PMID: 24516463
inducing medium; type III effector secretion; Xanthomonas
6.  Evaluation of a robot-assisted video-assisted thoracoscopic surgery programme 
At present, there is increasing interest in surgical procedures using a robot-assisted device. The aim of this study was to investigate whether robot-assisted video-assisted thoracoscopic surgery (VATS) was more effective than conventional VATS. A total of 64 VATS lobectomies in Papworth Hospital (Cambridge, UK) were included in the study. In 34 cases the lobectomies were performed using conventional VATS (CV group), while in the remaining 30 cases the lobectomies were performed using robot-assisted VATS (Robotic group). In the robot-assisted VATS, FreeHand®, a thoracoscopic camera controller produced by Freehand 2010 Ltd. (Eastleigh, UK), was used. The duration of the thoracoscopic surgery in the Robotic group was 145.50±10.43 min, whereas in the CV group the duration was 162.79±9.40 min. The surgery duration in the Robotic group was 10.62% shorter than that in the CV group (P<0.05). The rates of bleeding, pulmonary infection, arrhythmia and prolonged air leak (≥5 days) in the Robotic group were 0, 3.33, 26.67 and 13.33%, respectively, while the corresponding rates in the CV group were 2.94, 5.88, 20.59 and 17.65%, respectively. No significant differences were identified in the postoperative complication rates between the two groups (P≥0.05). There was no perioperative mortality in the study. Compared with conventional VATS, FreeHand-assisted VATS provides a similar rate of postoperative complications and a reduced surgery duration, and may be beneficial for the recovery of the patients following VATS.
PMCID: PMC3961121  PMID: 24669243
robot-assisted video-assisted thoracoscopic surgery; FreeHand; thoracoscopic camera holders
7.  An Approach for Identifying Brainstem Dopaminergic Pathways Using Resting State Functional MRI 
PLoS ONE  2014;9(1):e87109.
Here, we present an approach for identifying brainstem dopaminergic pathways using resting state functional MRI. In a group of healthy individuals, we searched for significant functional connectivity between dopamine-rich midbrain areas (substantia nigra; ventral tegmental area) and a striatal region (caudate) that was modulated by both a pharmacological challenge (the administration of the dopaminergic agonist bromocriptine) and a dopamine-sensitive cognitive trait (an individual’s working memory capacity). A significant inverted-U shaped connectivity pattern was found in a subset of midbrain-striatal connections, demonstrating that resting state fMRI data is sufficiently powerful to identify brainstem neuromodulatory brain networks.
PMCID: PMC3909040  PMID: 24498023
8.  Reliability and Repeatability of Quantitative Tractography Methods for Mapping Structural White Matter Connectivity in Preterm and Term Infants at Term-Equivalent Age 
PLoS ONE  2014;9(1):e85807.
Premature infants exhibit widespread insults and delays in white matter maturation that can be sensitively detected early using diffusion tensor imaging. Diffusion tensor tractography facilitates in vivo visualization of white matter tracts and has the potential to be more sensitive than simpler two-dimensional DTI-based measures. However, the reliability and reproducibility of performing tractography for major white matter tracts in preterm infants is not known. The main objective of our study was to develop highly reliable and repeatable methods for ten white matter tracts in extremely low birth weight infants (birth weight ≤1000 g) at term-equivalent age. To demonstrate clinical utility, we also compared fiber microstructural and macrostructural parameters between preterm and healthy term controls. Twenty-nine ELBW infants and a control group of 15 healthy term newborns were studied. A team of researchers experienced in neuroanatomy/neuroimaging established the manual segmentation protocol based on a priori anatomical knowledge and an extensive training period to identify sources of variability. Intra- and inter-rater reliability and repeatability was tested using intra-class correlation coefficient, within-subject standard deviation (SD), repeatability, and Dice similarity index. Our results support our primary goal of developing highly reliable and reproducible comprehensive methods for manual segmentation of 10 white matter tracts in ELBW infants. The within-subject SD was within 1–2% and repeatability within 3–7% of the mean values for all 10 tracts. The intra-rater Dice index was excellent with a range of 0.97 to 0.99, and as expected, the inter-rater Dice index was lower (range: 0.80 to 0.91), but still within a very good reliability range. ELBW infants exhibited fewer fiber numbers and/or abnormal microstructure in a majority of the ten quantified tracts, consistent with injury/delayed development. This protocol could serve as a valuable tool for prompt evaluation of the impact of neuroprotective therapies and as a prognostic biomarker for neurodevelopmental impairments.
PMCID: PMC3901659  PMID: 24475054
9.  Toward reliable characterization of functional homogeneity in the human brain: Preprocessing, scan duration, imaging resolution and computational space 
NeuroImage  2012;65:374-386.
While researchers have extensively characterized functional connectivity between brain regions, the characterization of functional homogeneity within a region of the brain connectome is in early stages of development. Several functional homogeneity measures were proposed previously, among which regional homogeneity (ReHo) was most widely used as a measure to characterize functional homogeneity of resting state fMRI (R-fMRI) signals within a small region (Zang et al., 2004). Despite a burgeoning literature on ReHo in the field of neuroimaging brain disorders, its test–retest (TRT) reliability remains unestablished. Using two sets of public R-fMRI TRT data, we systematically evaluated the ReHo’s TRT reliability and further investigated the various factors influencing its reliability and found: 1) nuisance (head motion, white matter, and cerebrospinal fluid) correction of R-fMRI time series can significantly improve the TRT reliability of ReHo while additional removal of global brain signal reduces its reliability, 2) spatial smoothing of R-fMRI time series artificially enhances ReHo intensity and influences its reliability, 3) surface-based R-fMRI computation largely improves the TRT reliability of ReHo, 4) a scan duration of 5 min can achieve reliable estimates of ReHo, and 5) fast sampling rates of R-fMRI dramatically increase the reliability of ReHo. Inspired by these findings and seeking a highly reliable approach to exploratory analysis of the human functional connectome, we established an R-fMRI pipeline to conduct ReHo computations in both 3-dimensions (volume) and 2-dimensions (surface).
PMCID: PMC3609711  PMID: 23085497
Connectome; Test–retest; Reliability; Functional homogeneity; Default network
10.  Morphologic and Functional Connectivity Alterations of Corticostriatal and Default Mode Network in Treatment-Naïve Patients with Obsessive-Compulsive Disorder 
PLoS ONE  2013;8(12):e83931.
Previous studies have demonstrated that structural deficits and functional connectivity imbalances might underlie the pathophysiology of obsessive-compulsive disorder (OCD). The purpose of the present study was to investigate gray matter deficits and abnormal resting-state networks in patients with OCD and further investigate the association between the anatomic and functional alterations and clinical symptoms.
Participants were 33 treatment-naïve OCD patients and 33 matched healthy controls. Voxel-based morphometry was used to investigate the regions with gray matter abnormalities and resting-state functional connectivity analysis was further conducted between each gray matter abnormal region and the remaining voxels in the brain.
Compared with healthy controls, patients with OCD showed significantly increased gray matter volume in the left caudate, left thalamus, and posterior cingulate cortex, as well as decreased gray matter volume in the bilateral medial orbitofrontal cortex, left anterior cingulate cortex, and left inferior frontal gyrus. By using the above morphologic deficits areas as seed regions, functional connectivity analysis found abnormal functional integration in the cortical-striatum-thalamic-cortical (CSTC) circuits and default mode network. Subsequent correlation analyses revealed that morphologic deficits in the left thalamus and increased functional connectivity within the CSTC circuits positively correlated with the total Y-BOCS score.
This study provides evidence that morphologic and functional alterations are seen in CSTC circuits and default mode network in treatment-naïve OCD patients. The association between symptom severity and the CSTC circuits suggests that anatomic and functional alterations in CSTC circuits are especially important in the pathophysiology of OCD.
PMCID: PMC3865285  PMID: 24358320
11.  Procalcitonin Levels Predict Acute Kidney Injury and Prognosis in Acute Pancreatitis: A Prospective Study 
PLoS ONE  2013;8(12):e82250.
Acute kidney injury (AKI) has been proposed as a leading cause of mortality for acute pancreatitis (AP) patients admitted to the intensive care unit (ICU). This study investigated the predictive value of procalcitonin (PCT) for AKI development and relevant prognosis in patients with AP, and compared PCT’s predictive power with that of other inflammation-related variables.
Between January 2011 and March 2013, we enrolled 305 cases with acute pancreatitis admitted to ICU. Serum levels of PCT, serum amyloid A (SAA), interleukin-6 (IL-6), and C reactive protein (CRP) were determined on admission. Serum PCT was tested in patients who developed AKI on the day of AKI occurrence and on either day 28 after occurrence (for survivors) or on the day of death (for those who died within 28 days).
Serum PCT levels were 100-fold higher in the AKI group than in the non-AKI group on the day of ICU admission (p<0.05). The area under the receiver-operating characteristic (ROC) curve of PCT for predicting AKI was 0.986, which was superior to SAA, CRP, and IL-6 (p<0.05). ROC analysis revealed all variables tested had lower predictive performance for AKI prognosis. The average serum PCT level on day 28 (2.67 (0.89, 7.99) ng/ml) was significantly (p<0.0001) lower than on the day of AKI occurrence (43.71 (19.24,65.69) ng/ml) in survivors, but the serum PCT level on death (63.73 (34.22,94.30) ng/ml) was higher than on the day of AKI occurrence (37.55 (18.70,74.12) ng/ml) in non-survivors, although there was no significant difference between the two days in the latter group (p = 0.1365).
Serum PCT is superior to CRP, IL-6, and SAA for predicting the development of AKI in patients with AP, and also can be used for dynamic evaluation of AKI prognosis.
PMCID: PMC3862675  PMID: 24349237
12.  Influence of APOE Genotype on Whole-Brain Functional Networks in Cognitively Normal Elderly 
PLoS ONE  2013;8(12):e83205.
This study aimed to investigate the influence of apolipoprotein E (APOE) ε4 allele on whole-brain functional networks in cognitively normal (CN) elderly by applying graph theoretical analysis to brain glucose metabolism. Eighty-six CN elderly [28 APOE ε4 carriers (ε4+) and 58 non-carriers (ε4-)] underwent clinical evaluation and resting [18F] fluorodeoxyglucose positron emission tomography scan. Whole-brain functional networks were constructed from correlations of the 90 regions of interest using the automated anatomical labeling template, and analyzed using graph theoretical approaches. The overall small-world property seen in ε4- was preserved in ε4+. However, both local clustering and path length were lower in ε4+ compared to ε4-. In terms of the hubs of functional networks, ε4+ showed decreased centrality of the right hippocampus but increased centrality of several brain regions associated with the default mode network compared to ε4-. Our results indicate that genetic vulnerability to Alzheimer’s disease may alter whole-brain functional networks even before clinical symptoms appear.
PMCID: PMC3859658  PMID: 24349461
13.  A Machine Learning Approach to Automated Structural Network Analysis: Application to Neonatal Encephalopathy 
PLoS ONE  2013;8(11):e78824.
Neonatal encephalopathy represents a heterogeneous group of conditions associated with life-long developmental disabilities and neurological deficits. Clinical measures and current anatomic brain imaging remain inadequate predictors of outcome in children with neonatal encephalopathy. Some studies have suggested that brain development and, therefore, brain connectivity may be altered in the subgroup of patients who subsequently go on to develop clinically significant neurological abnormalities. Large-scale structural brain connectivity networks constructed using diffusion tractography have been posited to reflect organizational differences in white matter architecture at the mesoscale, and thus offer a unique tool for characterizing brain development in patients with neonatal encephalopathy. In this manuscript we use diffusion tractography to construct structural networks for a cohort of patients with neonatal encephalopathy. We systematically map these networks to a high-dimensional space and then apply standard machine learning algorithms to predict neurological outcome in the cohort. Using nested cross-validation we demonstrate high prediction accuracy that is both statistically significant and robust over a broad range of thresholds. Our algorithm offers a novel tool to evaluate neonates at risk for developing neurological deficit. The described approach can be applied to any brain pathology that affects structural connectivity.
PMCID: PMC3840059  PMID: 24282501
14.  Successful treatment of bronchial obstruction by flexible bronchoscopy and isoniazid: A case report 
Interventional bronchology techniques have been employed as an effective first-line treatment in patients with tracheobronchial obstruction. However, recurrent stenosis produced by granulation tissue requires repeated procedures. Previous studies have indicated that isoniazid regulates collagen deposition and decreases collagen content. Thus, isoniazid has been successfully administered to patients with lesions who exhibited a delay in the healing process. A case of a left mainstem obstruction managed by interventional bronchology is described in the present study. Repeated bronchial stenosis was observed even following numerous treatment procedures, however, administration of isoniazid resulted in the inhibition of hypertrophic scar formation and prevention of repeated stenosis. The suppressive effect of isoniazid on granulation formation and further observations are reported. Few studies have been conducted with regard to the function of isoniazid in suppressing scar hyperplasia, therefore, the mechanism requires further investigation.
PMCID: PMC3881032  PMID: 24396413
interventional bronchologists; isoniazid; bronchial obstruction
15.  The correlation between morphology and the expression of TGF-β signaling pathway proteins and epithelial-mesenchymal transition-related proteins in synovial sarcomas 
Synovial sarcoma (SS) is a malignant tumor of soft tissue and is noted for late local recurrence and metastasis. Aberrant epithelial-mesenchymal transition (EMT) has been implicated in the pathogenesis of diverse human malignancies. Immunohistochemical techniques were used to assess EMT-related proteins (E-cadherin, N-cadherin, β-catenin, Snail, and Slug) and the TGF-β1 pathway (TGF-β1 and Smad2/3) proteins expression in different histological subtypes and epithelial mesenchymal compositions of SS. The expression of cell-surface (E-cadherin) and cytoskeletal proteins (β-catenin) were higher significantly in biphasic SSs (BSSs) (70.4%, 51.9%) than MFSSs (both for 10%). Among monophasic fibrous SSs (MFSSs) samples, E-cadherin protein expression was negatively correlated with expression Snail, Slug, TGF-β1, and Smad2/3. The expression levels of Snail and Smad2/3 were correlated with the pTNM stage (I-II vs. III-IV; P=0.047, P=0.021) and TGF-β1 exhibited a tendency toward a positive correlation with pTNM stage (I-II vs. III-IV; P=0.052), but did not correlate with the histological grade (p>0.05). Interestingly, our data showed that expression of E-cadherin protein correlated with greater survival in SS patients. Overexpression of Snail, and TGF-β1 is associated with suppressed expression of E-cadherin in MFSSs, which supports the hypothesis that the MFSS subtype may have developed via neoplastic EMT.
PMCID: PMC3843259  PMID: 24294365
Synovial sarcomas; epithelial-mesenchymal transition; TGF-β1 signaling pathway; immunohistochemistry
16.  Cyr61 is involved in neutrophil infiltration in joints by inducing IL-8 production by fibroblast-like synoviocytes in rheumatoid arthritis 
Arthritis Research & Therapy  2013;15(6):R187.
It is well known that neutrophils play very important roles in the development of rheumatoid arthritis (RA) and interleukin (IL)-8 is a critical chemokine in promoting neutrophil migration. We previously showed that increased production of Cyr61 by fibroblast-like synoviocytes (FLS) in RA promotes FLS proliferation and Th17 cell differentiation, thus Cyr61 is a pro-inflammatory factor in RA pathogenesis. In this study, we explored the role of Cyr61 in neutrophil migration to the joints of RA patients.
RA FLS were treated with Cyr61 and IL-8 expression was analyzed by real-time PCR and ELISA. The migration of neutrophils recruited by the culture supernatants was determined by the use of a chemotaxis assay. Mice with collagen-induced arthritis (CIA) were treated with anti-Cyr61 monoclonal antibodies (mAb), or IgG1 as a control. Arthritis severity was determined by visual examination of the paws and joint destruction was determined by hematoxylin-eosin (H&E) staining. Signal transduction pathways in Cyr61-induced IL-8 production were investigated by real-time PCR, western blotting, confocal microscopy, luciferase reporter assay or chromatin immunoprecipitation (ChIP) assay.
We found that Cyr61 induced IL-8 production by RA FLS in an IL-1β and TNF-α independent pathway. Moreover, we identified that Cyr61-induced IL-8-mediated neutrophil migration in vitro. Using a CIA animal model, we found that treatment with anti-Cyr61 mAb led to a reduction in MIP-2 (a counterpart of human IL-8) expression and decrease in neutrophil infiltration, which is consistent with an attenuation of inflammation in vivo. Mechanistically, we showed that Cyr61 induced IL-8 production in FLS via AKT, JNK and ERK1/2-dependent AP-1, C/EBPβ and NF-κB signaling pathways.
Our results here reveal a novel role of Cyr61 in the pathogenesis of RA. It promotes neutrophil infiltration via up-regulation of IL-8 production in FLS. Taken together with our previous work, this study provides further evidence that Cyr61 plays a key role in the vicious cycle formed by the interaction between infiltrating neutrophils, proliferated FLS and activated Th17 cells in the development of RA.
PMCID: PMC3978874  PMID: 24517278
17.  Building Kinetic Models for Determining Vitamin C Content in Fresh Jujube and Predicting Its Shelf Life Based on Near-Infrared Spectroscopy 
Sensors (Basel, Switzerland)  2013;13(11):15673-15681.
Fresh jujube (Ziziphus jujube) is rich in vitamin C, which is an important quality index and generally decreases with storage time. The aim of this study was to build kinetic models for determining the vitamin C content, thus predicting the quality characteristics and shelf life of fresh jujube. The quality changes of the jujube stored at room temperature (20 °C) were analyzed using near-infrared spectroscopy. The significant spectra were determined and a calibration model for vitamin C content was developed. The results showed that vitamin C content could be described by the zero-order kinetics model based on the regressions. In addition, the shelf life of the jujube at room temperature was calculated according to the regression model.
PMCID: PMC3871137  PMID: 24248281
fresh jujube; vitamin C content; kinetic model; shelf life; near-infrared spectroscopy
18.  MEK inhibition reduces glial scar formation and promotes the recovery of sensorimotor function in rats following spinal cord injury 
The aim of this study was to investigate the effect of U0126 on the formation of glial scars following spinal cord injury (SCI) in a rat model. Ninety adult female Sprague-Dawley rats were divided randomly into sham injury (group I), SCI (group II) and U0126 treatment (group III) groups, and functional outcome was observed during the 4 weeks following the injury. The P1 and N1 latencies and P1-N1 amplitudes of somatosensory-evoked potentials (SEPs) were collected one day prior to surgery, on the day of surgery and 14 and 28 days postoperatively. The expression levels of glial fibrillary acidic protein (GFAP) and vimentin (Vim) were assessed 14 and 28 days post-injury. Treatment with U0126 significantly increased locomotor function from the second week until 4 weeks post-SCI. At 14 and 28 days subsequent to the injury, the number of cells that were positive for GFAP expression in the U0126-treated group was significantly reduced and the GFAP-positive cells were observed to be smaller, with a reduced prominence and pale staining. Moreover, the area of glial scarring was smaller compared with that of the SCI controls. Inhibitors of MEK may reduce glial scar formation by suppressing the proliferation of astrocytes, and may improve hindlimb motor function.
PMCID: PMC3861407  PMID: 24348766
extracellular signal-regulated kinases; glial fibrillary acidic protein; spinal cord injury; glial scar; vimentin
19.  Regional Brain Atrophy and Functional Connectivity Changes Related to Fatigue in Multiple Sclerosis 
PLoS ONE  2013;8(10):e77914.
Fatigue is one of the most frequent symptoms in multiple sclerosis (MS), and recent studies have described a relationship between the sensorimotor cortex and its afferent and efferent pathways as a substrate of fatigue. The objectives of this study were to assess the neural correlates of fatigue in MS through gray matter (GM) and white matter (WM) atrophy, and resting state functional connectivity (rs-FC) of the sensorimotor network (SMN). Eighteen healthy controls (HCs) and 60 relapsing-remitting patients were assessed with the Fatigue Severity Scale (FSS). Patients were classified as fatigued (F) or nonfatigued (NF). We investigated GM and WM atrophy using voxel-based morphometry, and rs-FC changes with a seed-based method and independent component analysis (ICA). F patients showed extended GM and WM atrophy focused on areas related to the SMN. High FSS scores were associated with reductions of WM in the supplementary motor area. Seed analysis of GM atrophy in the SMN showed that HCs presented increased rs-FC between the primary motor and somatosensory cortices while patients with high FSS scores were associated with decreased rs-FC between the supplementary motor area and associative somatosensory cortex. ICA results showed that NF patients presented higher rs-FC in the primary motor cortex compared to HCs and in the premotor cortex compared to F patients. Atrophy reduced functional connectivity in SMN pathways and MS patients consequently experienced high levels of fatigue. On the contrary, NF patients experienced high synchronization in this network that could be interpreted as a compensatory mechanism to reduce fatigue sensation.
PMCID: PMC3805520  PMID: 24167590
20.  Fenofibrate Attenuated Glucose-Induced Mesangial Cells Proliferation and Extracellular Matrix Synthesis via PI3K/AKT and ERK1/2 
PLoS ONE  2013;8(10):e76836.
Excess mesangial extracellular matrix (ECM) and mesangial cell proliferation is the major pathologic feature of diabetic nephropathy (DN). Fenofibrate, a PPARα agonist, has been shown to attenuate extracellular matrix formation in diabetic nephropathy. However, the mechanisms underlying this effect remain to be elucidated. In this study, the effect of fenofibrate on high-glucose induced cell proliferation and extracellular matrix exertion and its mechanisms were investigated in cultured rat mesangial cells by the methylthiazoletetrazolium (MTT) assay, flow cytometry and western blot. The results showed that treatment of mesangial cells (MCs) with fenofibrate repressed high-glucose induced up-regulation of extracellular matrix Collagen-IV, and inhibited entry of cell cycle into the S phase. This G1 arrest and ECM inhibition was caused by the reduction of phosphorylation and activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and AKT. On the contrary, PPARα siRNA accelerated high glucose-induced cell cycle progression by ERK1/2 and AKT activation. Taken together, fenofibrate ameliorated glucose-induced mesangial cell proliferation and matrix production via its inhibition of PI3K/AKT and ERK1/2 signaling pathways. Such mechanisms may contribute to the favorable effects of treatment using fenofibrate in diabetic nephropathy.
PMCID: PMC3793917  PMID: 24130796
21.  Liver Ischemic Preconditioning (IPC) Improves Intestinal Microbiota Following Liver Transplantation in Rats through 16s rDNA-Based Analysis of Microbial Structure Shift 
PLoS ONE  2013;8(10):e75950.
Ischemia-reperfusion (I/R) injury is associated with intestinal microbial dysbiosis. The “gut-liver axis” closely links gut function and liver function in health and disease. Ischemic preconditioning (IPC) has been proven to reduce I/R injury in the surgery. This study aims to explore the effect of IPC on intestinal microbiota and to analyze characteristics of microbial structure shift following liver transplantation (LT).
The LT animal models of liver and gut IPC were established. Hepatic graft function was assessed by histology and serum ALT/AST. Intestinal barrier function was evaluated by mucosal ultrastructure, serum endotoxin, bacterial translocation, fecal sIgA content and serum TNF-α. Intestinal bacterial populations were determined by quantitative PCR. Microbial composition was characterized by DGGE and specific bacterial species were determined by sequence analysis.
Principal Findings
Liver IPC improved hepatic graft function expressed as ameliorated graft structure and reduced ALT/AST levels. After administration of liver IPC, intestinal mucosal ultrastructure improved, serum endotoxin and bacterial translocation mildly decreased, fecal sIgA content increased, and serum TNF-α decreased. Moreover, liver IPC promoted microbial restorations mainly through restoring Bifidobacterium spp., Clostridium clusters XI and Clostridium cluster XIVab on bacterial genus level. DGGE profiles indicated that liver IPC increased microbial diversity and species richness, and cluster analysis demonstrated that microbial structures were similar and clustered together between the NC group and Liver-IPC group. Furthermore, the phylogenetic tree of band sequences showed key bacteria corresponding to 10 key band classes of microbial structure shift induced by liver IPC, most of which were assigned to Bacteroidetes phylum.
Liver IPC cannot only improve hepatic graft function and intestinal barrier function, but also promote restorations of intestinal microbiota following LT, which may further benefit hepatic graft by positive feedback of the “gut-liver axis”.
PMCID: PMC3788797  PMID: 24098410
22.  Structures of native and Fe-substituted SOD2 from Saccharomyces cerevisiae  
The crystal structures of both native manganese SOD2 and iron-substituted SOD2 from S. cerevisiae were solved. The surface-potential properties showed a similar pattern to those of Cu/Zn-SODs.
The manganese-specific superoxide dismutase SOD2 from the yeast Saccharo­myces cerevisiae is a protein that resides in the mitochondrion and protects it against attack by superoxide radicals. However, a high iron concentration in the mitochondria results in iron misincorporation at the active site, with subsequent inactivation of SOD2. Here, the crystal structures of SOD2 bound with the native metal manganese and with the ‘wrong’ metal iron are presented at 2.05 and 1.79 Å resolution, respectively. Structural comparison of the two structures shows no significant conformational alteration in the overall structure or in the active site upon binding the non-native metal iron. Moreover, residues Asp163 and Lys80 are proposed to potentially be responsible for the metal specificity of the Mn-specific SOD. Additionally, the surface-potential distribution of SOD2 revealed a conserved positively charged electrostatic zone in the proximity of the active site that probably functions in the same way as in Cu/Zn-SODs by facilitating the diffusion of the superoxide anion to the metal ion.
PMCID: PMC3212356  PMID: 22102021
superoxide dismutases; Saccharomyces cerevisiae; SOD2
23.  Potential of Visible and Near Infrared Spectroscopy and Pattern Recognition for Rapid Quantification of Notoginseng Powder with Adulterants 
Sensors (Basel, Switzerland)  2013;13(10):13820-13834.
Notoginseng is a classical traditional Chinese medical herb, which is of high economic and medical value. Notoginseng powder (NP) could be easily adulterated with Sophora flavescens powder (SFP) or corn flour (CF), because of their similar tastes and appearances and much lower cost for these adulterants. The objective of this study is to quantify the NP content in adulterated NP by using a rapid and non-destructive visible and near infrared (Vis-NIR) spectroscopy method. Three wavelength ranges of visible spectra, short-wave near infrared spectra (SNIR) and long-wave near infrared spectra (LNIR) were separately used to establish the model based on two calibration methods of partial least square regression (PLSR) and least-squares support vector machines (LS-SVM), respectively. Competitive adaptive reweighted sampling (CARS) was conducted to identify the most important wavelengths/variables that had the greatest influence on the adulterant quantification throughout the whole wavelength range. The CARS-PLSR models based on LNIR were determined as the best models for the quantification of NP adulterated with SFP, CF, and their mixtures, in which the rP values were 0.940, 0.939, and 0.867 for the three models respectively. The research demonstrated the potential of the Vis-NIR spectroscopy technique for the rapid and non-destructive quantification of NP containing adulterants.
PMCID: PMC3859093  PMID: 24129019
spectral analysis; adulteration; chemometrics; least-square support vector machine (LS-SVM); partial least square regression (PLSR); competitive adaptive reweighted sampling (CARS)
24.  Early Exposure to Traumatic Stressors Impairs Emotional Brain Circuitry 
PLoS ONE  2013;8(9):e75524.
Exposure to early life trauma (ELT) is known to have a profound impact on mental development, leading to a higher risk for depression and anxiety. Our aim was to use multiple structural imaging methods to systematically investigate how traumatic stressors early in life impact the emotional brain circuits, typically found impaired with clinical diagnosis of depression and anxiety, across the lifespan in an otherwise healthy cohort. MRI data and self-reported histories of ELT from 352 healthy individuals screened for no psychiatric disorders were analyzed in this study. The volume and cortical thickness of the limbic and cingulate regions were assessed for all participants. A large subset of the cohort also had diffusion tensor imaging data, which was used to quantify white matter structural integrity of these regions. We found a significantly smaller amygdala volume and cortical thickness in the rostral anterior cingulate cortex associated with higher ELT exposure only for the adolescence group. White matter integrity of these regions was not affected. These findings demonstrate that exposure to early life trauma is associated with alterations in the gray matter of cingulate-limbic regions during adolescence in an otherwise healthy sample. These findings are interesting in the context that the affected regions are central neuroanatomical components in the psychopathology of depression, and adolescence is a peak period for risk and onset of the disorder.
PMCID: PMC3779182  PMID: 24073270
25.  Correction: A Hybrid CPU-GPU Accelerated Framework for Fast Mapping of High-Resolution Human Brain Connectome 
PLoS ONE  2013;8(9):10.1371/annotation/b93e8f81-3f0b-41d4-a725-0c54fd99d239.
PMCID: PMC3796586  PMID: 24137506

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