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2.  The role of miR-146a in dorsal root ganglia neurons of experimental diabetic peripheral neuropathy 
Neuroscience  2013;259:155-163.
Sensory neurons mediate diabetic peripheral neuropathy. Using a mouse model of diabetic peripheral neuropathy (db/db mice) and cultured dorsal root ganglion (DRG) neurons, the present study showed that hyperglycemia downregulated miR-146a expression and elevated interleukin-1 receptor activated kinase (IRAK1) and tumor necrosis factor receptor-associated factor 6 (TRAF6) levels in DRG neurons. In vitro, elevation of miR-146a by miR-146a mimics in DRG neurons increased neuronal survival under high glucose conditions. Downregulation and elevation of miR-146a in DRG neurons, respectively, were inversely related to IRAK1 and TRAF6 levels. Treatment of diabetic peripheral neuropathy with sildenafil, a phosphodiesterase type 5 inhibitor, augmented miR-146a expression and decreased levels of IRAK1 and TRAF6 in the DRG neurons. In vitro, blockage of miR-146a in DRG neurons abolished the effect of sildenafil on DRG neuron protection and downregulation of IRAK1 and TRAF6 proteins under hyperglycemia. Our data provide the first evidence showing that miR-146a plays an important role in mediating DRG neuron apoptosis under hyperglycemic conditions.
doi:10.1016/j.neuroscience.2013.11.057
PMCID: PMC3901076  PMID: 24316060
peripheral neuropathy; diabetes; mice; sildenafil; mir-146a
3.  The Emergence of Sex Differences in Personality Traits in Early Adolescence: A Cross-Sectional, Cross-Cultural Study 
Although large international studies have found consistent patterns of sex differences in personality traits among adults (i.e., women scoring higher on most facets), less is known about cross-cultural sex differences in adolescent personality and the role of culture and age in shaping them. The present study examines NEO Personality Inventory-3 (NEO-PI-3, McCrae, Costa, & Martin, 2005) informant ratings of adolescents from 23 cultures (N = 4,850) and investigates culture and age as sources of variability in sex differences of adolescents’ personality. The effect for Neuroticism (with females scoring higher than males) begins to take on its adult form around age 14. Girls score higher on Openness to Experience and Conscientiousness at all ages between 12 and 17 years. A more complex pattern emerges for Extraversion and Agreeableness, although by age 17, sex differences for these traits are highly similar to those observed in adulthood. Cross-sectional data suggest that (1) with advancing age, sex differences found in adolescents increasingly converge towards adult patterns with respect to both direction and magnitude; (2) girls display sex-typed personality traits at an earlier age than boys; and (3) the emergence of sex differences was similar across culture. Practical implications of the present findings are discussed.
doi:10.1037/a0038497
PMCID: PMC4327943  PMID: 25603371
Personality; Sex differences; Adolescence; Cross-cultural
4.  Complete genome sequence and transcriptomics analyses reveal pigment biosynthesis and regulatory mechanisms in an industrial strain, Monascus purpureus YY-1 
Scientific Reports  2015;5:8331.
Monascus has been used to produce natural colorants and food supplements for more than one thousand years, and approximately more than one billion people eat Monascus-fermented products during their daily life. In this study, using next-generation sequencing and optical mapping approaches, a 24.1-Mb complete genome of an industrial strain, Monascus purpureus YY-1, was obtained. This genome consists of eight chromosomes and 7,491 genes. Phylogenetic analysis at the genome level provides convincing evidence for the evolutionary position of M. purpureus. We provide the first comprehensive prediction of the biosynthetic pathway for Monascus pigment. Comparative genomic analyses show that the genome of M. purpureus is 13.6–40% smaller than those of closely related filamentous fungi and has undergone significant gene losses, most of which likely occurred during its specialized adaptation to starch-based foods. Comparative transcriptome analysis reveals that carbon starvation stress, resulting from the use of relatively low-quality carbon sources, contributes to the high yield of pigments by repressing central carbon metabolism and augmenting the acetyl-CoA pool. Our work provides important insights into the evolution of this economically important fungus and lays a foundation for future genetic manipulation and engineering of this strain.
doi:10.1038/srep08331
PMCID: PMC4321180  PMID: 25660389
5.  Effect of picroside II on apoptosis induced by renal ischemia/reperfusion injury in rats 
Renal ischemia and reperfusion (I/R) injury, which commonly occurs in kidney transplantation, is the leading cause of acute kidney injury. Picroside II possesses a wide range of pharmacological effects, including anti-apoptosis effects. In the present study, the ability of picroside II to attenuate apoptosis in a rat model of renal I/R injury was investigated. Sprague-Dawley rats were subjected to 45 min of ischemia followed by 24 h of reperfusion. Prior to reperfusion, the rats were treated with picroside II or an equal volume of phosphate-buffered saline. It was observed that renal function was significantly improved by the treatment with picroside II. Morphological analysis indicated that picroside II markedly reduced tissue damage and the expression of cleaved caspase-3. Reverse transcription-quantitative polymerase chain reaction and western blotting revealed that the expression levels of Bax and poly(ADP-ribose) polymerase-1 (PARP-1) were upregulated in the I/R group, whereas those of Bcl-2 were downregulated. However, the treatment with picroside II inhibited these changes induced by renal I/R injury. In conclusion, picroside II has potent anti-apoptotic activity against renal I/R injury.
doi:10.3892/etm.2015.2192
PMCID: PMC4316970  PMID: 25667634
picroside II; ischemia and reperfusion injury; apoptosis
6.  Disease-on-a-Chip: Mimicry of Tumor Growth in Mammary Ducts 
Lab on a chip  2013;14(1):10.1039/c3lc50819f.
We present a disease-on-a-chip model in which cancer grows within phenotypically normal breast luminal epithelium on semicircular acrylic support mimicking portions of mammary ducts. The cells from tumor nodules developing within these hemichannels are morphologically distinct from their counterparts cultured on flat surfaces. Moreover, tumor nodules cocultured with the luminal epithelium in hemichannels display a different anticancer drug sensitivity compared to nodules cocultured with the luminal epithelium on a flat surface and to monocultures of tumor nodules. The mimicry of tumor development within the epithelial environment of mammary ducts provides a framework for the design and test of anticancer therapies.
doi:10.1039/c3lc50819f
PMCID: PMC3880579  PMID: 24202525
7.  A mutation associated with centronuclear myopathy enhances the size and stability of dynamin 2 complexes in cells 
Biochimica et biophysica acta  2013;1840(1):10.1016/j.bbagen.2013.09.001.
Background
Dynamin 2 (Dyn2) is a ~100 kDa GTPase that assembles around the necks of nascent endocytic and Golgi vesicles and catalyzes membrane scission. Mutations in Dyn2 that cause Centronuclear Myopathy (CNM) have been shown to stabilize Dyn2 polymers against GTP-dependent disassembly in vitro. Precisely timed regulation of assembly and disassembly is believed to be critical for Dyn2 function in membrane vesiculation, and the CNM mutations interfere with this regulation by shifting the equilibrium toward the assembled state.
Methods
In this study we use two fluorescence fluctuation spectroscopy (FFS) approaches to show that a CNM mutant form of Dyn2 also has a greater propensity to self-assemble in the cytosol and on the plasma membrane of living cells.
Results
Results obtained using brightness analysis indicate that unassembled wild-type Dyn2 is predominantly tetrameric in the cytosol, although different oligomeric species are observed, depending on the concentration of expressed protein. In contrast, an R369W mutant identified in CNM patients forms higher-order oligomers at concentrations above 1 μM. Investigation of Dyn2-R369W by Total Internal Reflection Fluorescence (TIRF) FFS reveals that this mutant forms larger and more stable clathrin-containing structures on the plasma membrane than wild-type Dyn2.
Conclusions and General Significance
These observations may explain defects in membrane trafficking reported in CNM patient cells and in heterologous systems expressing CNM-associated Dyn2 mutants.
doi:10.1016/j.bbagen.2013.09.001
PMCID: PMC3859711  PMID: 24016602
Dynamin 2; Centronuclear myopathy; R369W mutation; EGFP; Fluorescence Fluctuation Spectroscopy; TIRF
8.  Nondisclosure of HIV Status in a Clinical Trial Setting: Antiretroviral Drug Screening Can Help Distinguish Between Newly Diagnosed and Previously Diagnosed HIV Infection 
In The HIV Prevention Trials Network 061 study, 155 human immunodeficiency virus (HIV)–infected men reported no prior HIV diagnosis; 83 of those men had HIV RNA levels of <1000 copies/mL at enrollment. Antiretroviral drug testing revealed that 65 of the 83 (78.3%) men were on antiretroviral treatment. Antiretroviral drug testing can help distinguish between newly diagnosed and previously diagnosed HIV infection.
doi:10.1093/cid/cit672
PMCID: PMC3864502  PMID: 24092804
HIV; antiretroviral; self-report; MSM; new diagnosis
9.  Identification and Functional Analysis of a Novel Tryptophyllin Peptide from the Skin of the Red-eye Leaf Frog, Agalychnis callidryas 
Amphibian skin has proved repeatedly to be a largely untapped source of bioactive peptides and this is especially true of members of the Phyllomedusinae subfamily of frogs native to South and Central America. Tryptophyllins are a group of peptides mainly found in the skin of members of this genus. In this study, a novel tryptophyllin (TPH) type 3 peptide, named AcT-3, has been isolated and structurally-characterised from the skin secretion and lyophilised skin extract of the red-eye leaf frog, Agalychnis callidryas. The peptide was identified in and purified from the skin secretion by reverse-phase HPLC. MALDI-TOF mass spectrometry and MS/MS fragmentation sequencing established its primary structure as: pGlu-Gly-Lys-Pro-Tyr-Trp-Pro-Pro-Pro-Phe-Leu-Pro-Glu, with a non-protonated molecular mass of 1538.19Da. The mature peptide possessed the canonical N-terminal pGlu residue that arises from post-translational modification of a Gln residue. The deduced open-reading frame consisted of 63 amino acid residues encoding a highly-conserved signal peptide of approximately 22 amino acid residues, an intervening acidic spacer peptide domain, a single AcT-3 encoding domain and a C terminal processing site. A synthetic replicate of AcT-3 was found to antagonise the effect of BK on rat tail artery smooth muscle and to contract the intestinal smooth muscle preparations. It was also found that AcT-3 could dose-dependently inhibit the proliferation of human prostate cancer cell lines after 72h incubation.
doi:10.7150/ijbs.10143
PMCID: PMC4279096  PMID: 25561903
Agalychnis callidryas; proline-rich peptide; bradykinin antagonist; anticancer effect; myotropic activities
10.  Changes in Follicular Helper T Cells in Idiopathic Thrombocytopenic Purpura Patients 
Background: Idiopathic thrombocytopenic purpura (ITP) is a primary autoimmune disease with a decreased platelet count caused by platelet destruction mediated mainly by platelet antibodies. T follicular helper (TFH) cells have demonstrated important roles in autoimmune diseases. The aim of this study is to explore the might role of TFH cells in the patients of ITP.
Methods: Twenty-three ITP patients and 12 healthy controls (HC) were enrolled in this study. The frequency of circulating TFH cells in both the patients and HC was analyzed by flow cytometry. Serum interleukin (IL)-21 and IL-6 levels were measured using ELISA, and platelet antibodies were tested using a solid phase technique. Additionally, IL-21, IL-6, Bcl-6 and c-Maf mRNA expressions in peripheral blood mononuclear cells (PBMCs) were detected using real-time PCR.
Results: The percentages of circulating CXCR5+ CD4+TFH cells with ICOShigh or PD-1high expression were significantly higher in the ITP patients than in the HC. Moreover, the frequencies of circulating CXCR5+ CD4+TFH cells with inducible costimulator (ICOS)high or programmed death-1 (PD-1)high expression were notably higher in ITP with platelet-antibody-positive ( ITP (+) ) patients than in ITP with platelet-antibody-negative ( ITP (-) ) patients and HC, as were the serum IL-21 and IL-6 levels (significant). Moreover, a positive correlation was found between the CXCR5+CD4+TFH cells with ICOShigh or PD-1high expression and the serum IL-21 levels of ITP (+) patients. Additionally, the mRNA expression levels of IL-21, IL-6, Bcl-6 and c-Maf were significantly increased in ITP patients, especially in ITP (+) patients.
Conclusions: This study demonstrated TFH cells and effector molecules might play an important role in the pathogenesis of ITP, which are possible therapeutic targets in ITP patients.
doi:10.7150/ijbs.10178
PMCID: PMC4279097  PMID: 25561904
platelet antibody; T follicular helper cell; idiopathic thrombocytopenic purpura; autoimmune disease
11.  Increased ARPP-19 Expression Is Associated with Hepatocellular Carcinoma 
The cAMP-regulated phosphoprotein 19 (ARPP-19) plays a key role in cell mitotic G2/M transition. Expression of ARPP-19 was increased in human hepatocellular carcinoma (HCC) compared to adjacent non-tumorous liver tissues in 36 paired liver samples, and the level of ARPP-19 in HCC tissues was positively correlated with the tumor size. To determine the interrelationship between ARPP-19 expression and HCC, we silenced ARPP-19 expression in the human hepatocarcinoma HepG2 and SMMC-7721 cells using lentivirus encoding ARPP-19 siRNA. HepG2 and SMMC-7721 cells with ARPP-19 knockdown displayed lowered cell growth rate, retarded colony formation and increased arrest at the G2/M phase transition. Silencing ARPP-19 in HCC cells resulted in decreased protein levels of phospho-(Ser) CDKs substrates and increased levels of inactivated cyclin division cycle 2 (Cdc2). Therefore, ARPP-19 may play a role in HCC pathogenesis through regulating cell proliferation.
doi:10.3390/ijms16010178
PMCID: PMC4307242  PMID: 25547487
hepatocellular carcinoma; ARPP-19; cell proliferation; cell cycle
12.  Comparison of Combined General-Epidural Anesthesia with General Anesthesia Effects on Survival and Cancer Recurrence: A Meta-Analysis of Retrospective and Prospective Studies 
PLoS ONE  2014;9(12):e114667.
Objective
Animals underwent combined general-epidural anesthesia (EGA) is reported to have better long-time outcome than general anesthesia (GA). This study aimed to make overall evaluation of the association between these two anesthetic techniques and prognosis of cancer patients undergoing surgery.
Methods
Related databases such as PubMed and EMbase were searched for eligible studies that evaluated the influence of EGA and GA on the prognosis of cancer patients undergoing surgery. Selected studies were evaluated according to the inclusion criteria by two reviewers respectively, followed by data extraction and quality assessment. The odds ratio (OR) with their 95% confidence intervals (CIs) were calculated to assess the influence strength of EGA and GA on prognosis of cancer patients.
Results
A total of ten studies involving 3254 patients were included. The overall results demonstrated that there was no significant difference between EGA and GA group (OR = 0.88, 95% CI 0.73 to 1.06, P = 0.187) concerning postoperative recurrence and metastasis rate. In regard to the following two factors: cancer category and time of follow-up, subgroup analysis identified significant differences between EGA and GA in the group of patients with prostate cancer and the group with follow-up less than or equal to two years (OR = 0.66, 95% CI 0.46 to 0.95, P = 0.027; OR = 0.70, 95% CI 0.51 to 0.98, P = 0.035; respectively) concerning postoperative recurrence and metastasis rate. However, no significant difference was found in the group of patients with colorectal cancer (OR = 1.06, 95% CI 0.84–1.33, P = 0.62).
Conclusions
This meta-analysis showed that EGA might be associated with improvement in prognosis of patients with operable prostate cancer and the cancer patients with follow-up less than or equal to two years. However, no obvious relationship between the improvement in prognosis of colorectal cancer and EGA were detected, comparing to GA. Furthermore, all the results should be interpreted cautiously, as heterogeneous data were used for analyzing.
doi:10.1371/journal.pone.0114667
PMCID: PMC4280190  PMID: 25548913
13.  Distance-based classifiers as potential diagnostic and prediction tools for human diseases 
BMC Genomics  2014;15(Suppl 12):S10.
Typically, gene expression biomarkers are being discovered in course of high-throughput experiments, for example, RNAseq or microarray profiling. Analytic pipelines that extract so-called signatures suffer from the "Dimensionality curse": the number of genes expressed exceeds the number of patients we can enroll in the study and use to train the discriminator algorithm. Hence, problems with the reproducibility of gene signatures are more common than not; when the algorithm is executed using a different training set, the resulting diagnostic signature may turn out to be completely different.
In this paper we propose an alternative novel approach which takes into account quantifiable expression levels of all genes assayed. In our analysis, the cumulative gene expression pattern of an individual patient is represented as a point in the multidimensional space formed by all gene expression profiles assayed in given system, where the clusters of "normal samples" and "affected samples" and defined. The degree of separation of the given sample from the space occupied by "normal samples" reflects the drift of the sample away from homeostasis in the course of development of the pathophysiological process that underly the disease. The outlined approach was validated using the publicly available glioma dataset deposited in Rembrandt and associated with survival data. Additionally, the applicability of the distance analysis to the classification of non-malignant sampled was tested using psoriatic lesions and non-lesional matched controls as a model.
Keywords: biomarkers; clustering; human diseases; RNA
doi:10.1186/1471-2164-15-S12-S10
PMCID: PMC4303935  PMID: 25563076
14.  A versatile platform to analyze low affinity and transient protein-protein interactions in living cells in real time 
Cell reports  2014;9(5):1946-1958.
SUMMARY
Protein-protein interactions (PPIs) play central roles in orchestrating biological processes. While some PPIs are stable, many important ones are transient and hard to detect with conventional approaches. We developed ReBiL, a recombinase enhanced bimolecular luciferase complementation platform, to enable weak PPI detection in living cells. ReBiL readily identified challenging transient interactions between an E3 ubiquitin ligase and an E2 ubiquitin-conjugating enzyme. ReBiL’s ability to rapidly interrogate PPIs in diverse conditions revealed that some stapled α-helical peptides, a new class of PPI antagonists, induce target-independent cytosolic leakage and cytotoxicity that is antagonized by serum. These results explain the requirement for serum-free conditions to detect stapled peptide activity, and define a required parameter to evaluate for peptide antagonist approaches. ReBiL’s ability to expedite PPI analysis, assess target specificity and cell permeability, and to reveal off-target effects of PPI modifiers should facilitate development of effective, cell permeable PPI therapeutics and elaboration of diverse biological mechanisms.
doi:10.1016/j.celrep.2014.10.058
PMCID: PMC4269221  PMID: 25464845
P53; Mdm2; Mdm4; Ube2t; FANCL; Bimolecular luciferase complementation; BiLC; Protein-fragment complementation assay; PCA; Recombinase mediated cassette exchange; RMCE; Protein-protein interaction; PPI; Recombinase enhanced BiLC; ReBiL; Stapled peptide; Nutlin-3a
15.  Expression of NALPs in adipose and the fibrotic progression of non-alcoholic fatty liver disease in obese subjects 
BMC Gastroenterology  2014;14(1):208.
Background
Visceral obesity is often accompanied by non-alcoholic fatty liver disease (NAFLD). Activation of NACHT, LRR and PYD domains-containing proteins (NALPs) may contribute to the release of pro-inflammatory cytokines by adipose and the obesity-associated progression of NAFLD to non-alcoholic steatohepatitis (NASH).
Methods
We analyzed visceral adipose expression of various NALPs and its downstream effectors caspase-1, ASC (Apoptosis-associated speck-like protein containing a CARD), IL-18 (Interleukin-18) and IL-1β (Interleukin- 1Beta) in obese subjects (BMI ≥ 35) with biopsy proven NAFLD.
Results
In adipose samples collected from NASH and pericellular fibrosis patients cohorts, expression levels of NALPs and IL-1β were lower than that in non-NASH patients. In portal fibrosis, the levels of mRNA encoding anti-inflammatory NALP6 were upregulated. The expression levels of all NALPs were significantly co-correlated. Circulating IL-18 levels were associated with increased liver injury markers AST and ALT and portal fibrosis.
Conclusion
Our observations point at a possible shift in inflammation and fibrotic response from adipose tissue to liver and a possible negative feedback regulation of tissue inflammation that may instigate NAFLD severity.
Electronic supplementary material
The online version of this article (doi:10.1186/s12876-014-0208-8) contains supplementary material, which is available to authorized users.
doi:10.1186/s12876-014-0208-8
PMCID: PMC4279907  PMID: 25512222
Obesity; NAFLD; Inflammasomes; Cytokines; Fibrosis
16.  Primary clear cell carcinoma of nasal cavity: report of six cases and review of literature 
Aims: This study is to retrospectively analyze the clinical and pathological data of six cases of primary nasal clear cell carcinoma in our hospital since 1992 and to review literatures on the clinical manifestations, pathological features, immunohistochemistry, diagnosis and treatment of the disease. Methods: The pathological archives that were diagnosed as salivary gland nasal tumors in Shandong Cancer Hospital during 1992-2013 were reviewed. Careful review of sections was performed by two experienced pathologists. The samples were labeled using EnVision method. Immunostaining was performed using 3, 3’-diaminobenzidine reagent followed by counterstaining with hematoxylin. The immunohistochemical results were classified according to positive cells: no positive staining cells (-); positive cells <30% (+); positive cells between 30% and 50% (++); and positive cells >50% (+++). Results: Among the 6 cases of primary nasal clear cell carcinoma in our hospital since 1992, 4 cases were diagnosed as clear cell carcinoma of nasal cavity after exclusion of other nasal cavity tumors with clear cells, and 2 cases were directly diagnosed as clear cell carcinoma of nasal cavity. Hyalinizing clear cell carcinoma of salivary gland (HCCC) tissues were mainly composed of polygonal epithelioid tumor cells arranged into the shapes of beehives, and separated by fibrous tissues containing rich thin-wall capillaries. The cytoplasm of HCCC cells was rich and translucent with some cells having multiple vacuoles. Reticular fiber staining showed that the tumor cells were arranged in shapes of beehives and separated by rich reticular fibers. HCCC tumor reacted differently on S-100 protein, glial fibrillary acidic protein, actin and vimentin. The ultrastructure of HCCC cells showed characteristics of ducts but no myoepithelial differentiation. Conclusions: This study demonstrates that correct diagnosis, timely surgical resection and postoperative radiotherapy are effective in treating nasal clear cell carcinoma.
PMCID: PMC4307504  PMID: 25664057
Primary clear cell carcinoma; nasal cavity; hyalinizing clear cell carcinoma of salivary gland
17.  Expression level of serum human epididymis 4 and its prognostic significance in human non-small cell lung cancer 
The prognostic significance of serum human epididymis protein 4 (HE4) levels in human NSCLC among a Chinese population has not been investigated. The purpose of this study was to evaluate the prognostic significance of serum HE4 level in patients with NSCLC among a Chinese population. Serum HE4 expression levels were measured by enzyme-linked immunosorbent assay (ELISA). The overall survival (OS) analyzed by log-rank test, and survival curves was plotted according to Kaplan-Meier. The COX proportional hazards regression model was used to determine the joint effects of several variables on survival. Serum HE4 level was found to be significantly higher in patients with NSCLC than that of controls (13.76 ± 5.01 ng/ml vs. 5.09 ± 1.25 ng/ml, P < 0.01). High HE4 expression was correlated with TNM stage (P = 0.003), lymph node metastases (P = 0.007), and distant metastases (P < 0.001). Furthermore, patients with high serum HE4 level had a significantly lower 5-year OS rate (34.0% vs. 59.7%; P = 0.022) than those with low serum HE4 level. In a multivariate Cox model, we found that HE4 expression was an independent poor prognostic factor for 5-year OS (hazards ratio [HR] = 3.654, 95% confidence interval [CI] = 2.753-11.981, P = 0.019) in NSCLC. In conclusion, the detection of HE4 levels in the serum might serve as a new tumor biomarker in the prognosis of NSCLC among Chinese population.
PMCID: PMC4307520  PMID: 25664073
Lung cancer; prognosis; HE4; serum; marker
18.  Genetically Encoded Chemical Probes In Cells Reveal the Binding Path of Urocortin-I to CRF Class B GPCR 
Cell  2013;155(6):1258-1269.
SUMMARY
Molecular determinants regulating the activation of class B G-protein coupled receptors (GPCRs) by native peptide agonists are largely unknown. We have investigated here the interaction between the corticotropin releasing factor receptor type 1 (CRF1R) and its native 40-mer peptide ligand Urocortin-I directly in mammalian cells. By incorporating unnatural amino acid photo-chemical and new click-chemical probes into the receptor, 44 inter-molecular spatial constraints have been derived for the ligand-receptor interaction. The data were analyzed in the context of the recently resolved crystal structure of CRF1R transmembrane domain and existing extracellular domain structures, yielding a complete conformational model for the peptide-receptor complex. Structural features of the receptor-ligand complex yield molecular insights on the mechanism of receptor activation. The experimental strategy provides unique information on full-length post-translationally modified GPCRs in the native membrane of the live cell, complementing in vitro biophysical reductionist approaches.
doi:10.1016/j.cell.2013.11.008
PMCID: PMC3916339  PMID: 24290358
19.  Cingulate Gyrus Neuroanatomy in Schizophrenia Subjects and Their Non-Psychotic Siblings 
Schizophrenia research  2008;104(0):61-70.
Background and Methods
In vivo neuroimaging studies have provided evidence of decreases in the gray matter volume of the cingulate gyrus in subjects with schizophrenia as compared to healthy controls. To investigate whether these changes might be related to heritable influences, we used high resolution magnetic resonance imaging and labeled cortical mantle distance mapping to measure gray matter volume, as well as thickness and the area of the gray/white interface, in the anterior and posterior segments of the cingulate gyrus in 28 subjects with schizophrenia and their non-psychotic siblings, and in 38 healthy control subjects and their siblings.
Results
There was a significant effect of group status on posterior cingulate cortex (PCC) gray matter volume (p=0.02). Subjects with schizophrenia and their non-psychotic siblings showed similar reductions of gray matter volume (∼10%) in the PCC compared to healthy control subjects and their siblings. In turn, trend level effects of group status were found for thickness (p=0.08) and surface area (p=0.11) of the PCC. In the combined group of schizophrenia subjects and their siblings, a direct correlation was observed between PCC gray matter volume and negative symptoms. However, the reduction in PCC gray matter volume in schizophrenia subjects and their siblings was proportionate to an overall reduction in whole cerebral volume, i.e., the effect of group on the volume of the PCC became non-significant when cerebral volume was included as a covariate (p=0.4). There was no significant effect of group on anterior cingulate cortex volume, thickness, or area.
Conclusions
Our findings suggest that decreases in the gray matter volume of the PCC occur in schizophrenia subjects and their siblings. The presence of such decreases in the non-psychotic siblings of schizophrenia subjects suggests that heritable factors may be involved in the development of cortical abnormalities in schizophrenia.
doi:10.1016/j.schres.2008.06.014
PMCID: PMC4256942  PMID: 18692994
cingulate; schizophrenia; volume; thickness; cortex; sibling; depth mapping
20.  A New Oligonucleotide Microarray for Detection of Pathogenic and Non-Pathogenic Legionella spp. 
PLoS ONE  2014;9(12):e113863.
Legionella pneumophila has been recognized as the major cause of legionellosis since the discovery of the deadly disease. Legionella spp. other than L. pneumophila were later found to be responsible to many non-pneumophila infections. The non-L. pneumophila infections are likely under-detected because of a lack of effective diagnosis. In this report, we have sequenced the 16S-23S rRNA gene internal transcribed spacer (ITS) of 10 Legionella species and subspecies, including L. anisa, L. bozemanii, L. dumoffii, L. fairfieldensis, L. gormanii, L. jordanis, L. maceachernii, L. micdadei, L. pneumophila subspp. fraseri and L. pneumophila subspp. pasculleii, and developed a rapid oligonucleotide microarray detection technique accordingly to identify 12 most common Legionella spp., which consist of 11 pathogenic species of L. anisa, L. bozemanii, L. dumoffii, L. gormanii, L. jordanis, L. longbeachae, L. maceachernii, L. micdadei, and L. pneumophila (including subspp. pneumophila, subspp. fraseri, and subspp. pasculleii) and one non-pathogenic species, L. fairfieldensis. Twenty-nine probes that reproducibly detected multiple Legionella species with high specificity were included in the array. A total of 52 strains, including 30 target pathogens and 22 non-target bacteria, were used to verify the oligonucleotide microarray assay. The sensitivity of the detection was at 1.0 ng with genomic DNA or 13 CFU/100 mL with Legionella cultures. The microarray detected seven samples of air conditioner-condensed water with 100% accuracy, validating the technique as a promising method for applications in basic microbiology, clinical diagnosis, food safety, and epidemiological surveillance. The phylogenetic study based on the ITS has also revealed that the non-pathogenic L. fairfieldensis is the closest to L. pneumophila than the nine other pathogenic Legionella spp.
doi:10.1371/journal.pone.0113863
PMCID: PMC4254607  PMID: 25469776
21.  Excessive levels of nitric oxide in rat model of Parkinson’s disease induced by rotenone 
Systemic rotenone models of Parkinson’s disease (PD) are highly reproducible and may provide evidence on the pathogenesis of PD. In the present study, male Sprague-Dawley rats (1-year-old) were subcutaneously administered with rotenone (1.5 mg/kg/day) for six days and observed for the following three weeks. Compared with the control rats, a significant decrease was observed in the body weight and a marked increase was observed in the areas under the behavioral scoring curves in the rotenone-treated rats. Immunohistochemical staining revealed that the abundance of nigral tyrosine hydroxylase (TH)-positive neurons was markedly reduced following rotenone treatment. ELISA and neurochemical assays demonstrated a significant increase in the levels of nitric oxide (NO) and NO synthase, whereas a marked decrease was observed in the thiol levels in the brains of the rotenone-treated rats. Thus, subacute rotenone treatment was found to induce behavioral deficits and the loss of nigral TH-positive neurons which may be associated with the excessive levels of NO in the rat brains.
doi:10.3892/etm.2014.2099
PMCID: PMC4280943  PMID: 25574233
nitric oxide; rotenone; Parkinson’s disease
22.  The Inaccuracy of National Character Stereotypes 
Journal of research in personality  2013;47(6):10.1016/j.jrp.2013.08.006.
Consensual stereotypes of some groups are relatively accurate, whereas others are not. Previous work suggesting that national character stereotypes are inaccurate has been criticized on several grounds. In this article we (a) provide arguments for the validity of assessed national mean trait levels as criteria for evaluating stereotype accuracy; and (b) report new data on national character in 26 cultures from descriptions (N=3,323) of the typical male or female adolescent, adult, or old person in each. The average ratings were internally consistent and converged with independent stereotypes of the typical culture member, but were weakly related to objective assessments of personality. We argue that this conclusion is consistent with the broader literature on the inaccuracy of national character stereotypes.
doi:10.1016/j.jrp.2013.08.006
PMCID: PMC3811946  PMID: 24187394
National character; stereotypes; Five-Factor Model; personality traits; cross-cultural
23.  Differences in Substance Use, Psychosocial Characteristics and HIV-Related Sexual Risk Behavior Between Black Men Who Have Sex with Men Only (BMSMO) and Black Men Who Have Sex with Men and Women (BMSMW) in Six US Cities 
We assessed associations in substance use, psychosocial characteristics, and HIV-related sexual risk behaviors, comparing characteristics of Black men who only have sex with other men only (BMSMO; n = 839) to Black men who have sex with men and women (BMSMW; n = 590). The study analyzed baseline data from the HIV Prevention Trials Network Brothers Study (HPTN 061), a feasibility study of a multi-component intervention for Black MSM in six US cities. Bivariate analyses compared BMSMO to BMSMW along demographics, substance use, psychosocial characteristics, and HIV-related sexual risk behaviors. Logistic regression models then assessed multivariable associations between being BMSMW and the odds of engaging in HIV-related sexual risk behaviors. Adjusted analyses revealed that BMSMW remained more likely to have unprotected anal intercourse while under the influence of alcohol (AOR: 1.45; 95 % CI:1.11–1.90) and were more likely to receive money/drugs for sex (AOR: 2.11; 95 % CI:1.48–3.03), compared to BMSMO. Substance use is an important factor to be considered when developing risk-reduction interventions for BMSMW. Structural interventions that address factors that may contribute to exchange sex among these men are also warranted.
doi:10.1007/s11524-013-9811-1
PMCID: PMC3853182  PMID: 23897039
HIV; Black MSM; Substance use; Mental health; Homophobia; Sexual risk; Sexual minorities
24.  Interleukin 17A Promotes Pneumococcal Clearance by Recruiting Neutrophils and Inducing Apoptosis through a p38 Mitogen-Activated Protein Kinase-Dependent Mechanism in Acute Otitis Media 
Infection and Immunity  2014;82(6):2368-2377.
Streptococcus pneumoniae is a Gram-positive and human-restricted pathogen colonizing the nasopharynx with an absence of clinical symptoms as well as a major pathogen causing otitis media (OM), one of the most common childhood infections. Upon bacterial infection, neutrophils are rapidly activated and recruited to the infected site, acting as the frontline defender against emerging microbial pathogens via different ways. Evidence shows that interleukin 17A (IL-17A), a neutrophil-inducing factor, plays important roles in the immune responses in several diseases. However, its function in response to S. pneumoniae OM remains unclear. In this study, the function of IL-17A in response to S. pneumoniae OM was examined using an in vivo model. We developed a model of acute OM (AOM) in C57BL/6 mice and found that neutrophils were the dominant immune cells that infiltrated to the middle ear cavity (MEC) and contributed to bacterial clearance. Using IL-17A knockout (KO) mice, we found that IL-17A boosted neutrophil recruitment to the MEC and afterwards induced apoptosis, which was identified to be conducive to bacterial clearance. In addition, our observation suggested that the p38 mitogen-activated protein kinase (MAPK) signaling pathway was involved in the recruitment and apoptosis of neutrophils mediated by IL-17A. These data support the conclusion that IL-17A contributes to the host immune response against S. pneumoniae by promoting neutrophil recruitment and apoptosis through the p38 MAPK signaling pathway.
doi:10.1128/IAI.00006-14
PMCID: PMC4019148  PMID: 24664502
25.  Association of IL-27 gene three polymorphisms with Crohn’s disease susceptibility in a Chinese Han population 
Objective: To investigate the association of three polymorphisms in the Interleukin-27 (IL-27) gene with CD risk in Chinese population. Methods: This case-control study involved 312 CD patients and 479 age- and sex-matched healthy controls. Genotyping was performed using PCR-LDR method. Data were analyzed using Haplo. Stats program. Results: There were significant differences between patients and controls in allele distributions of rs153109 (Pallele = 0.036). The risk for CD associated with the rs153109-G mutant allele was increased by 26% (95% CI [confidence interval]: 1.02-1.56; P = 0.03) under the additive model and by 45% (95% CI: 1.07-1.97; P = 0.02) under the dominant model. In haplotype analysis, haplotype T-T-G (in order of rs17855750, rs181206 and rs153109) increased the odds of CD by 37% (95% CI: 1.04-1.81; P = 0.028). Conclusions: In conclusion, genetic defects in IL-27 gene showed remarkable associations with CD in Chinese.
PMCID: PMC4313976
IL-27; polymorphism; Crohn’s diseases; susceptibility; association study

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