In birds, activation of the aryl hydrocarbon receptor (AhR) by some polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) results in induction of cytochrome P4501A (CYP1A) expression. This response has been useful for predicting relative sensitivity of birds to dioxin-like compounds. To further investigate species-sensitivity to dioxins and dioxin-like compounds induction of cytochrome P450 1A4 and 1A5 (CYP1A4 and CYP1A5) mRNA and ethoxyresorufin O-deethylase (EROD) activity were quantified in liver of posthatch white leghorn chicken, common pheasant, and Japanese quail exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,3,4,7,8-pentachlorodibenzofuran (PeCDF), or 2,3,7,8-tetrachlorodibenzofuran (TCDF) via air cell injection. The rank-order of sensitivity of TCDD- and TCDF-exposed birds, based on CYP1A, was chicken > pheasant > quail. Based on CYP1A5 mRNA expression and EROD induction, the order of sensitivity of PeCDF-exposed birds was identical to that for TCDD and TCDF. However, based on CYP1A4 mRNA expression the rank-order was pheasant > chicken > quail. When comparing the potency of the three compounds in each species, based on CYP1A4 mRNA expression, TCDD was the most potent compound in chicken. However, PeCDF was equally potent to TCDD in quail and was more potent than TCDD in pheasant. These results suggest that quantitative real-time polymerase chain reaction (Q-PCR) analysis of CYP1A expression, particularly CYP1A4 mRNA expression, may be a more sensitive biomarker of exposure than analysis of EROD induction, especially in less responsive avian species. Based on these findings future risk assessments should consider the sensitivity of the species inhabiting a site and the congeners of concern that are present. Environ. Toxicol. Chem. 2010;29:1490-1502. (c) 2010 SETAC.

Historical opinions of the "species problem" are briefly reviewed, and four salient stages are recognized according to origin of species concepts. We propose that species is the unit preserving superior gene assembly and is maintained by specific mechanisms. Based on characteristics of plant evolution, we assume that understanding plant species may include three stages, i.e. morphological recognition stage, multidisciplinary verification stage, and illuminating mechanisms preserving superior gene assembly.

A transverse piezoelectric field-effect transistor (TP-FET) based on single ZnO nanobelts has been fabricated on a metallic graphite substrate in an atomic force microscope (AFM). The source-to-drain current of the TP-FET was found to decrease with increasing loading force under a positive bias due to the carrier-trapping effect and the creation of a charge-depletion zone. This TP-FET can be applied as a force/pressure sensor for measuring nanoNewton forces ranged from 0 to 700 nN.

This study investigated the transfection ability and efficiency of liposomes and immunoliposomes for exogenous gene delivery into the brain via the venous system. Four groups of rats underwent tail vein injection with one of the following: liposomes encapsulating pCMV (human cytomegalovirus promoter)-LacZ plasmid 80 mug (low dose) or 300 mug (high dose); general immunoliposomes encapsulating 80 mug transferrin receptor antibodies (OX26)-pCMV-LacZ plasmid; or brain-specific immunoliposomes encapsulating 80 mug OX26-pGFAP (glial fibrillary acidic protein promoter)-LacZ plasmid. A control group received no injected agent. The LacZ mRNA levels (1 h post-injection) and beta-galactosidase activity (48 h post-injection) in the brain and peripheral organs were assayed using real-time reverse transcription-polymerase chain reaction and histochemical staining, respectively. Both immunoliposomes delivered exogenous DNA containing the LacZ gene into the brain after venous injection, resulting in extensive LacZ expression in the brain. Furthermore, the brain-specific OX26-pGFAP-LacZ immunoliposome decreased the non-specific expression of LacZ in peripheral organs without affecting transfection efficiency in the brain. Thus, brain-specific immunoliposomes are an efficient and brain-specific targeting vector.

Summary. Seroconversion from hepatitis B surface antigen (HBsAg) to antibodies against HBsAg (anti-HBs) usually indicates resolution of hepatitis B virus (HBV) infection. Here, two HBV-infected patients with seroconversion to anti-HBs were found to be persistently positive for HBeAg and HBV DNA. Immunohistology of liver biopsies confirmed the expression of HBV proteins in the liver of one patient. The neutralizing ability of anti-HBs in patient sera was demonstrated by blocking HBV infection of primary tupaia hepatocytes. Analysis of the HBsAg-encoding region of HBV isolates from patients indicated the coexistence of heterogeneous HBV genomes in patients. The majority of recombinant variant HBsAg was reactive in HBsAg assays and was able to bind to anti-HBs. Circulating immune complexes (CIC) of HBsAg in patient sera could be detected by polyethylene glycol precipitation and trypsin digestion. Thus, neutralizing anti-HBs may appear in chronic HBV carriers for long periods but does not necessarily lead to complete viral clearance.

The response mechanism of a simple device for the rapid detection of ketamine with 'in the field' capabilities is investigated. The mechanism is a membranous ketamine ionic selective electrode (ISE) with partly carboxylated PVC as matrix and ortho-nitrophenyloctyl ether (o-NPOE) as plasticizer. The experimental results reveal that the inclusion of the plasticizer in the membrane significantly increased the response. A mechanism is proposed where the infiltration of a target species into the membrane is capable of producing a superior response. This response process is non-selective for species with similar molecular structure and size. This new research addresses some omissions and misapprehension in the literature where the mechanism was reported as an ion-exchange-induced response. In this research the ion-exchange-induced response was measurable after the elimination of the infiltration-induced response extending to lower concentration ranges and thus providing the potential for better sensitivity and selectivity. Copyright (c) 2010 John Wiley & Sons, Ltd.

OBJECTIVE: Cortical thickness reductions in prefrontal and temporal cortices have been repeatedly observed in patients with schizophrenia. However, it remains unclear whether regional variations in cortical thickness may be attributable to disease-related or genetic-liability factors. METHOD: The structural magnetic resonance imaging data of 48 adult-onset schizophrenia patients, 66 first-degree non-psychotic relatives of schizophrenia patients, 27 community comparison (CC) probands and 77 CC relatives were examined using cortical pattern matching methods to map and compare highly localized changes in cortical gray matter thickness between groups defined by biological risk for schizophrenia. RESULTS: Schizophrenia patients showed marked cortical thinning primarily in frontal and temporal cortices when compared to unrelated CC probands. Results were similar, though less pronounced when patients were compared with their non-psychotic relatives. Cortical thickness reductions observed in unaffected relatives compared to age-similar CC relatives suggestive of schizophrenia-related genetic liability were marginal, surviving correction for the left parahippocampal gyrus and inferior occipital cortex only. CONCLUSIONS: Observations of pronounced fronto/temporal cortical thinning in schizophrenia patients replicate prior findings. The lack of marked cortical thickness alterations in non-psychotic relatives of patients, suggests that disease processes are primary contributors toward cortical thickness reductions in the disorder. However, genetic factors may have a larger influence on abnormalities in the medial temporal lobe.

MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression at the post-transcriptional and/or translational level by binding loosely complimentary sequences in the 3'untranslated regions (UTRs) of target mRNAs. Increased expression of several miRNAs, specifically hsa-miR-21, have been reported to modulate glioma development. Here we report downregulation of miR-451 in A172, LN229 and U251 human glioblastoma cells. Increased expression of miR-451 by administration of miR-451 mimics oligonucleotides reversed the biology of each of the three cell lines, inhibiting cell growth, inducing G0/G1 phase arrest and increasing cell apoptosis. Further, treatment with miR-451 mimics oligonucleotides diminished the invasive capacity of these cells, as the number of cells invading through matrigel was significantly decreased. Akt1, CyclinD1, MMP-2, MMP-9 and Bcl-2 protein expression decreased, and p27 expression increased in a dose-dependent manner with miR-451 mimics oligonucleotides. Taken together, these studies reveal miR-451 impacts glioblastoma cell proliferation, invasion and apoptosis, perhaps via regulation of the PI3K/AKT signaling pathway. We propose an essential role for miR-451 as a tumor-suppressor of human glioma.

BACKGROUND AND AIMS:: Esophageal cancer is the 6 (th) leading cause of cancer death worldwide, and the most common form, esophageal squamous cell cancer, comprising more than 90% of cases, is precipitated by factors that provoke chronic epithelial irritation. Yet the molecular mediators of esophageal epithelial inflammation and the processes driving carcinogenesis are largely unknown, at least in part because squamous cell cancer has been extraordinarily difficult to model genetically in vivo. METHODS:: We utilized the ED-L2promoter of Epstein-Barr virus to overexpress the transcriptional regulator Klf4in esophageal epithelia of mice and used mouse primary esophageal keratinocytes to mechanistically examine the effects of KLF4 on cytokine induction. RESULTS:: By overexpressing Klf4in esophageal epithelia of mice, we identified a novel function for KLF4 as an epithelial-specific inflammatory mediator and generated a faithful model of human esophageal squamous dysplasia and inflammation-mediated squamous cell cancer. Moreover, we showed that KLF4 activates a number of proinflammatory cytokines, including TNF-alpha, CXCL5, G-CSF and IL-1alpha, within keratinocytes in an NF-kappaB dependent manner. We also found that KLF4 was excluded from proliferating and cancer cells, suggesting a non-cell autonomous effect of KLF4 on proliferation and carcinogenesis. CONCLUSIONS:: Our results demonstrate that KLF4 can perform distinct functions in oncogenesis within a single tissue. Further, we show that upregulation of Klf4specifically within epithelial cells provokes inflammation and provides a valuable model with which to dissect the molecular pathways underlying inflammation and carcinogenesis in vivo.

Protein O-mannose N-acetylglucosaminyltransferase 1 (POMGnT1) is an enzyme that catalyzes the transfer of N-acetylglucosamine to O-mannose of glycoproteins. It is involved in posttranslational modification of alpha-dystroglycan (alpha-DG). POMGnT1-null mice were generated by gene trapping with a retroviral vector inserted into exon 2 of the POMGnT1 gene. Expression of POMGnT1 was completely disrupted as evidenced by absence of its mRNA expression. POMGnT1 knockout mice were viable but with reduced fertility and variable lifespan. The functional glycosylated form of alpha-DG was markedly reduced in POMGnT1 knockout mice along with impaired alpha-DG-laminin binding activity. Multiple developmental defects in muscle, brain, and eye were observed. In addition, the knockout mice exhibited extensive abnormalities in the neocortex, including changed neuron distribution, presence of ectopic fibroblasts, and GFAP-positive reactive astrocytes. Analysis of POMGnT1 knockout neocortex at several developmental stages revealed that these defects were secondary to disruptions of the pial basement membrane.

OBJECTIVE: The authors studied the lifetime prevalence of DSM-IV-TR psychiatric disorders in a population of adults with the fragile X premutation. METHOD: The Structured Clinical Interview for DSM-IV was conducted, from 2007-2008, in 85 individuals with the fragile X premutation, 47 with the fragile X-associated tremor/ataxia syndrome (FXTAS; 33 male, 14 female; mean age = 66 years) and 38 without FXTAS (16 male, 22 female; mean age = 52 years). Lifetime prevalence for mood and anxiety disorders among carriers with and without FXTAS was compared to available age-specific population estimates from the National Comorbidity Survey Replication (NCS-R). RESULTS: Among participants with FXTAS, 30 (65%) met lifetime DSM-IV-TR criteria for a mood disorder; 24 (52%) met lifetime DSM-IV-TR criteria for an anxiety disorder. Among the non-FXTAS participants, there were 15 instances of lifetime mood disorder (42%) and 18 of lifetime anxiety disorder (47%). When compared to age-specific NCS-R data, the lifetime prevalences of any mood disorder (P < .0001), major depressive disorder (P < .0001), any anxiety disorder (P < .0001), panic disorder (P = .006), specific phobia (P = .0003), and posttraumatic stress disorder (P = .004) were significantly higher in participants with FXTAS. The lifetime rates of social phobia in individuals with the premutation without FXTAS were significantly higher than NCS-R data (P = .001). CONCLUSIONS: This sample of carriers of the fragile X premutation had a notably high lifetime risk of mood and anxiety disorders. Mood and anxiety disorders may be part of the clinical phenotype of the fragile X premutation conditions, especially in carriers with FXTAS. Clinicians encountering these patients are advised to consider FXTAS as a neuropsychiatric syndrome as well as a neurologic disorder.

Ultrafast transient absorption spectroscopy was used to investigate the photochemistry of adenosylcobalamin (AdoCbl), methylcobalamin (MeCbl), and n-propylcobalamin (PrCbl) at pH 2 where the axial nitrogenous ligand is replaced by a water molecule. The evolution of the difference spectrum reveals the internal conversion process and spectral characteristics of the S(1) excited state. The photolysis yield in the base-off cobalamins is controlled by competition between internal conversion and bond homolysis. This is in direct contrast to the process in most base-on alkylcobalamins where primary photolysis occurs with near unit quantum yield and the photolysis yield is controlled by competition between diffusive separation of the radical pair and geminate recombination. The absence of the axial nitrogenous ligand in the base-off cobalamins modifies the electronic structure and opens a channel for fast nonradiative decay. This channel competes effectively with the channel for bond dissociation, dropping the quantum yield for primary radical pair formation from unity in base-on PrCbl and AdoCbl to 0.2 +/- 0.1 and 0.12 +/- 0.06 in base-off PrCbl and AdoCbl, respectively. The photolysis of base-off MeCbl is similar to that of base-off AdoCbl and PrCbl with competition between rapid nonradiative decay leading to ground state recovery and formation of a radical pair following bond homolysis.

OBJECTIVE: To explore whether polyethylene glycol (PEG) as adjuvant could enhance the humoral and cellular immune responses on hepatitis B virus DNA vaccine. METHODS: C57BL/6J mice were immunized with PEG and pVAX-S2 or alone pVAX-S2. After these mice were finally immunized for 14 days, the anti-HBs IgG, T cell proliferation, the expression of cytokines and CTL in vivo were detected. RESULTS: Compared to mice immunized with alone pVAX-S2, PEG as adjuvant could increase the production of anti-HBs IgG and HBsAg specific T cell proliferation. In addition, the expression of IL-4, IFN-gamma in CD4+ T cells and IFN-gamma in CD8+ T cells was higher than control groups. The PEG/ pVAX-S2 groups could elicit significantly in vivo HBsAg specific CTL responses. CONCLUSIONS: PEG as adjuvant could enhance humoral and cellular immune responses, as well as in vivo CTL activity.

Microbial fuel cells (MFCs) are bio-electrochemical reactors that have the capacity to convert chemical energy of biodegradable organic chemicals to electrical energy, and developed rapidly in the past few years. With an increasing concern for energy crisis and environment pollution, MFCs has became a promising technology in the researches of environment pollution treatments and biology electricity. In this paper, we offered a comprehensive review of the recent research progress of MFCs in environment pollution treatment, includes denitrification, desufurization, organic pollutants degradation, heavy metal reduction and landfill leachate treatment. Also, we pointed out the challenges and problems which were bottle necks for a wide application of MFCs and the potential future development.

Aggregative adherence fimbriae (AAF) are the primary adhesive factors of enteroaggregative Escherichia coli (EAEC) and are required for intestinal colonization. They mediate binding to extracellular matrix proteins of the enteric mucosa and display proinflammatory effects on epithelial cells in vitro. Among the simplest of bacterial fimbriae, these passive hairlike appendages are composed primarily of a single 16-kDa structural and adhesive subunit, AafA. Oligomerization occurs by incorporating the N-terminal strand of each AafA subunit into an otherwise incomplete beta-sheet of an adjacent AafA subunit. We have engineered a highly soluble AafA monomer by positioning the N-terminal "donor strand" at the C-terminus, following a turn and short linker that were introduced to allow access of the donor strand to the recipient cleft of the same subunit. The resulting "donor-strand complemented" AafA subunit, or AafA-dsc folds autonomously, is monodisperse in solution, and yields high quality NMR spectral data. Here, we report the (1)H, (13)C, and (15)N chemical shift assignments for AafA-dsc.

OBJECTIVE: To investigate the correlation of cytokeratin pan (CKP), vascular endothelial growth factor (VEGF) expression and microvessel density (MVD) to spiral CT manifestations of thymoma. METHODS: Eighty-four thymoma patients were underwent spiral CT examination, and 40 of the patients also had enhanced CT examination. All the CT findings were carefully reviewed to analyze their correlation to the expressions of CKP, VEGF and MVD. RESULTS: The enhancement on spiral CT images increased with the levels of VEGF expression and MVD counting (P<0.01). Significant correlations were observed between VEGF expression, MVD counting and such spiral CT findings as lobular contours, cusp-like or sawtooth-like margins and tumor invasions of the pleural membrane, pericardium and great vessels (P<0.05). CKP expression showed no obvious correlation to these findings by spiral CT. CONCLUSION: Spiral CT can reflect the pathological characteristics of thymoma, and may serve as a noninvasive modality for preoperative evaluation of thymoma.

The pro-oncogene FBI-1, encoded by Zbtb7a, is a transcriptional repressor that belongs to the POK (POZ/BTB and Krüppel) protein family. In this study, we investigated a potential interaction between androgen receptor (AR) signaling and FBI-1 and demonstrated that overexpression of FBI-1 inhibited ligand-dependent AR activation. A protein-protein interaction was identified between FBI-1 and AR in a ligand-dependent manner. Furthermore, FBI-1, AR and SMRT formed a ternary complex and FBI-1 enhanced the recruitment of NCoR and SMRT to endogenous PSA upstream sequences. Our data also indicated that the FBI-1-mediated inhibition of AR transcriptional activity is partially dependent on HDAC. Interestingly, FBI-1 plays distinct roles in regulating LNCaP (androgen-dependent) and PC-3 cell (androgen-independent) proliferation.

Special AT-rich sequence binding protein 1 (SATB1), a new type of gene regulator, has been reported to express in various human cancers and may associate with the malignant potential. However, there are few data available on SATB1 expression and its relationship to tumor progression in gastric cancer. The current study was designed to examine the SATB1 expression in gastric cancer and to correlate it with clinical outcome. SATB1 expression was studied by qRT-PCR, western blotting and immunohistochemistry, respectively. The correlations between SATB1 expression and clinicopathological factors were statistically analyzed. SATB1 mRNA expression was significantly up-regulated in gastric cancer specimens as compared with that in normal tissues (P<0.001). Overexpression of SATB1 protein was observed in gastric cancer cell lines by western blotting. Fifty-three (44.9%) cases showed positive staining for the SATB1 proteins by immunohistochemistry. The expression of SATB1 mRNA agreed well with the western blotting and immunohistochemical findings (P<0.001). SATB1 expression was positively correlated with age, depth of invasion, lymph node metastasis, distant metastasis and TNM stage. Moreover, Kaplan-Meier analysis revealed that SATB1 overexpression was associated with a significantly worse survival (P<0.001). Further multivariable analysis indicated that SATB1 expression was an independent prognostic indicator for gastric cancer (P=0.023). In summary, overexpression of SATB1 correlated with metastatic potential of human gastric cancer and would be a novel independent prognostic marker for predicting the outcome of gastric cancer.

BACKGROUND & AIMS: Certain liver diseases have been associated with depletion of glutathione (GSH), the major antioxidant in liver. A recent report about Gclc(h/h) mice with a hepatocyte-specific ablation of Gclc (the gene encoding the catalytic subunit of the rate-limiting enzyme in GSH synthesis) has shown an essential role of GSH in hepatic function. Gclc(h/h) mice develop severe steatosis and die of liver failure within one month, due to approximately 95% depletion of hepatic GSH; mitochondria are the major affected organelles, displaying abnormal ultrastructure and impaired functioning. METHODS: Gclc(h/h) mice were fed with L-N-acetylcysteine (NAC; 10g/L) in drinking water, starting at postnatal day 18. RESULTS: Gclc(h/h) mice were rescued by use of NAC supplementation, and survived until adulthood. NAC replenished the mitochondrial GSH pool and attenuated mitochondrial damage, with accompanying diminished hepatic steatosis; however, abnormal liver biochemical tests, hepatocyte death, and hepatic oxidative stress persisted in the rescued mice. At 50days of age, the liver from rescued Gclc(h/h) mice started to display characteristics of fibrosis and at age 120days, macronodular cirrhosis was observed. Immunohistostaining for liver-specific markers as well as the expression profile of hepatic cytokines indicated that the repopulation of hepatocytes in the cirrhotic nodules involved the expansion of oval cells. CONCLUSIONS: Replenishment of mitochondrial GSH and restoration of mitochondrial function by NAC prevents mortality caused by the loss of hepatocyte GSH de novo synthesis, allowing steatosis to progress to a chronic stage. Thus, with NAC supplementation, Gclc(h/h) mice provide a model for the development of liver fibrosis and cirrhosis.