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author:("Zhao, livia")
1.  Strong enhancement of photoresponsivity with shrinking the electrodes spacing in few layer GaSe photodetectors 
Scientific Reports  2015;5:8130.
A critical challenge for the integration of optoelectronics is that photodetectors have relatively poor sensitivities at the nanometer scale. Generally, a large electrodes spacing in photodetectors is required to absorb sufficient light to maintain high photoresponsivity and reduce the dark current. However, this will limit the optoelectronic integration density. Through spatially resolved photocurrent investigation, we find that the photocurrent in metal-semiconductor-metal (MSM) photodetectors based on layered GaSe is mainly generated from the region close to the metal-GaSe interface with higher electrical potential. The photoresponsivity monotonically increases with shrinking the spacing distance before the direct tunneling happens, which was significantly enhanced up to 5,000 AW−1 for the bottom Ti/Au contacted device. It is more than 1,700-fold improvement over the previously reported results. The response time of the Ti/Au contacted devices is about 10–20 ms and reduced down to 270 μs for the devices with single layer graphene as metallic electrodes. A theoretical model has been developed to well explain the photoresponsivity for these two types of device configurations. Our findings realize reducing the size and improving the performance of 2D semiconductor based MSM photodetectors simultaneously, which could pave the way for future high density integration of optoelectronics with high performances.
PMCID: PMC4311250  PMID: 25632886
2.  The effect of UGTs polymorphism on the auto-induction phase II metabolism-mediated pharmacokinetics of dihydroartemisinin in healthy Chinese subjects after oral administration of a fixed combination of dihydroartemisinin-piperaquine 
Malaria Journal  2014;13(1):478.
Dihydroartemisinin (DHA) is a component of artemisinin-based combination therapy (ACT), which is widely recommended for treatment of uncomplicated falciparum malaria. DHA is also the main metabolite of artemether and artesunate, both of which are used in ACT. Due to auto-induction metabolism, declining plasma concentrations after the repeated dosing have been reported for artemisinin (Qing-hao-su) and artemether. This study was designed to evaluate the potential auto-induction metabolism of DHA in healthy Chinese adults after multiple oral doses of DHA. The polymorphic effects of UGT1A9 (I399C>T) and UGT2B7*2 (802C>T), the major enzymes involved in the metabolism of DHA, on the pharmacokinetic profiles of DHA and its metabolite was also studied.
Sixteen healthy Chinese subjects (four I399TT/802CC, four I399CC/802TT, four I399TT/802TT and four I399CT/802CT) received four recommended oral doses of Artekin, an ACT containing DHA (80 mg/dose) and piperaquine (PQ; 640 mg/dose), at 0, 6, 24 and 32 h. Plasma samples were analysed for DHA and its metabolite using a validated liquid chromatography tandem mass spectrometric (LC-MS) method.
DHA and its glucuronidated metabolite DHA-Glu were detected in human plasma after oral administration of DHA-PQ. Compared with the first dose, the AUC0-t of the parent drug DHA decreased significantly (P<0.01) with increased oral clearance (CL/F) after each repeated dose of DHA-PQ, whereas its metabolite DHA-Glu did not change (P>0.05) in AUC0-t or Cmax. The phase II metabolic capability, calculated by the AUC0-t ratio of DHA-Glu to the parent drug DHA, increased 1.5-fold (90% CI, 1.3-1.7), 1.2-fold (90% CI, 1.1-1.3) and 1.7-fold (90% CI, 1.5-1.8) after the second, third and fourth dose, respectively. No polymorphic effect was found for UGT1A9 (I399C>T) and UGT2B7*2 (802C>T) on the pharmacokinetic profiles of DHA and its metabolite DHA-Glu.
The auto-induction phase II metabolism of DHA was present in healthy Chinese subjects after the recommended two-day oral doses of DHA-PQ (Artekin). The metabolic capability could recover after a 12-h dosing interval, which suggested that the alternative common three-day regimen (once daily) for DHA-PQ could probably lead to higher bioavailability of DHA. The polymorphism of UGT1A9 (I399C>T) and UGT2B7*2 (802C>T) may not be a concern during the treatment with DHA.
Electronic supplementary material
The online version of this article (doi:10.1186/1475-2875-13-478) contains supplementary material, which is available to authorized users.
PMCID: PMC4265406  PMID: 25476790
Dihydroartemisinin; Auto-induction metabolism; Healthy Chinese; UGTs; Polymorphism
3.  A new 5-grading score in the diagnosis of prostate cancer with real-time elastography 
Objective: To evaluate the clinical significance of transrectal real-time elastography (TRTE) in diagnosis of prostate cancer (PCA). Methods: 195 patients with an elevated PSA level were enrolled in the study. A novel 5-grading score of prostate outer gland was applied by TRTE imaging. Receiver-operating characteristic curve (ROC) analyses were performed to assess the diagnostic performance of TRTE score. Results: TRTE scores in patients with PCA and benign condition were 3.20 ± 1.11 (range: 1-5) and 2.24 ± 1.01 (range: 1-4), respectively (P < 0.001). The best cutoff value of TRTE score was 3, and the sensitivity, specificity, accuracy in the diagnosis were 68.6% (35/51), 69.4% (100/144) and 69.2% (135/195), respectively. The accuracy of TRTE in volume ≤ 30 ml group was significantly higher than that in the volume ≥ 50 ml group and the 30-50 ml group (76.9% vs. 65.0% and 76.9% vs. 71.4%, both P < 0.001). Accuracy of TRTE score was higher for those with PSA ranged 4-10 ng/ml than those with PSA > 10 ng/ml (85.3% vs. 66.7%, P = 0.002). Conclusion: TRTE score, a novel semi-quantitative assessment of patients’ prostate stiffness, can be served as a useful screening method for patients suspicious of PCA, especially those only having an elevated PSA level.
PMCID: PMC4129027  PMID: 25120792
Prostate cancer; transrectal real-time elastography
5.  IL-1β and TNF-α induce neurotoxicity through glutamate production: a potential role for neuronal glutaminase 
Journal of neurochemistry  2013;125(6):897-908.
Glutaminase 1 is the main enzyme responsible for glutamate production in mammalian cells. The roles of macrophage and microglia glutaminases in brain injury, infection, and inflammation are well documented. However, little is known about the regulation of neuronal glutaminase, despite neurons being a predominant cell type of glutaminase expression. Using primary rat and human neuronal cultures, we confirmed that interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), two proinflammatory cytokines that are typically elevated in neurodegenerative disease states, induced neuronal death and apoptosis in vitro. Furthermore, both intracellular and extracellular glutamate levels were significantly elevated following IL-1β and/or TNF-α treatment. Pretreatment with N-Methyl-D-aspartate (NMDA) receptor antagonist MK-801 blocked cytokine-induced glutamate production and alleviated the neurotoxicity, indicating that IL-1β and/or TNF-α induce neurotoxicity through glutamate. To determine the potential source of excess glutamate production in the culture during inflammation, we investigated the neuronal glutaminase and found that treatment with IL-1β or TNF-α significantly upregulated the kidney type glutaminase (KGA), a glutaminase 1 isoform, in primary human neurons. The upregulation of neuronal glutaminase was also demonstrated in situ in a murine model of HIV-1 encephalitis. In addition, IL-1β or TNF-α treatment increased the levels of KGA in cytosol and TNF-α specifically increased KGA levels in the extracellular fluid, away from its main residence in mitochondria. Together, these findings support neuronal glutaminase as a potential component of neurotoxicity during inflammation and that modulation of glutaminase may provide therapeutic avenues for neurodegenerative diseases.
PMCID: PMC3747774  PMID: 23578284
Inflammation; glutaminase; glutamate; neurotoxicity
6.  CXCL12 Enhances Human Neural Progenitor Cell Survival through a CXCR7- and CXCR4- mediated Endocytotic Signaling Pathway 
Stem cells (Dayton, Ohio)  2012;30(11):2571-2583.
Chemokine CXCL12 is widely expressed in the central nervous system (CNS) and essential for the proper functions of human neural progenitor cells (hNPCs). Although CXCL12 is known to function through its receptor CXCR4, recent data have suggested that CXCL12 binds to chemokine receptor CXCR7 with higher affinity than to CXCR4. However, little is known about the function of CXCR7 in hNPCs. Using a primary hNPC culture system, we demonstrated that CXCL12 promotes hNPC survival in the events of camptothecin-induced apoptosis or growth factor deprivation, and that this effect requires both CXCR7 and CXCR4. Through FACS analysis and immunocytochemistry, we determined that CXCR7 is mainly localized in the early endosome, while CXCR4 is more broadly expressed at the cell surface and on both early and recycling endosomes. Furthermore, we found that endocytosis is required for the pro-survival function of CXCL12. Using dual-color Total Internal Reflection Fluorescence microscopy and immunoprecipitation, we demonstrated that CXCR7 quickly trafficks to plasma membrane in mediating CXCL12 endocytosis and colocalizes with CXCR4 after CXCL12 treatment. Investigating the molecular mechanisms, we found that ERK1/2 endocytotic signaling pathway is essential for hNPC survival upon apoptotic challenges. Consistent with these findings, a significantly higher number of apoptotic NPCs were found in the developing brain of CXCR7 knockout mice. In conclusion, CXCL12 protects hNPCs from apoptotic challenges through CXCR7- and CXCR4-mediated endocytotic signaling. Since survival of hNPCs is important for neurogenesis, CXCR7 may become a new therapeutic target to properly regulate critical processes of brain development.
PMCID: PMC3969741  PMID: 22987307
7.  Anoctamin 6 Regulates C2C12 Myoblast Proliferation 
PLoS ONE  2014;9(3):e92749.
Anoctamin 6 (Ano6) belongs to a conserved gene family (TMEM16) predicted to code for eight transmembrane proteins with putative Ca2+-activated chloride channel (CaCC) activity. Recent work revealed that disruption of ANO6 leads to a blood coagulation defect and impaired skeletal development. However, its function in skeletal muscle cells remains to be determined. By using a RNA interference mediated (RNAi) loss-of-function approach, we show that Ano6 regulates C2C12 myoblast proliferation. Ano6 is highly expressed in C2C12 myoblasts and its expression decreases upon differentiation. Knocking down Ano6 significantly reduces C2C12 myoblast proliferation but has minimal effect on differentiation. Ano6 deficiency significantly reduces ERK/AKT phosphorylation, which has been shown to be involved in regulation of cancer cell proliferation by another Anoctamin member. Taken together, our data demonstrate for the first time that Ano6 plays an essential role in C2C12 myoblast proliferation, likely via regulating the ERK/AKT signaling pathway.
PMCID: PMC3963950  PMID: 24663380
8.  STAT1 Regulates Human Glutaminase 1 Promoter Activity through Multiple Binding Sites in HIV-1 Infected Macrophages 
PLoS ONE  2013;8(9):e76581.
Mononuclear phagocytes (MP, macrophages and microglia), the main targets of HIV-1 infection in the brain, play a pathogenic role in HIV-associated neurocognitive disorders (HAND) through the production and release of various soluble neurotoxic factors including glutamate. We have previously reported that glutaminase (GLS), the glutamate-generating enzyme, is upregulated in HIV-1 infected MP and in the brain tissues of HIV dementia individuals, and that HIV-1 or interferon-α (IFN-α) regulates human glutaminase 1 (GLS1) promoter through signal transducer and activator of transcription 1 (STAT1) phosphorylation in macrophages. However, there are multiple putative STAT1 binding sites in human GLS1 promoter, the exact molecular mechanism of how HIV-1 or IFN-α regulates human GLS1 promoter remains unclear. To further study the function of the putative STAT1 binding sites, we mutated the sequence of each binding site to ACTAGTCTC and found that six mutants (mut 1,3,4,5,7,8) had significantly higher promoter activity and two mutants (mut 2 and mut 6) completely lost the promoter activity compared with the wild type. To determine whether sites 2 and 6 could interfere with other inhibitory sites, particularly the nearby inhibitory sites 3 and 5, we made double mutants dmut 2/3 and dmut 5/6, and found that both the double mutants had significantly higher activity than the wild type, indicating that sites 3 and 5 are critical inhibitory elements, while sites 2 and 6 are excitatory elements. ChIP assay verified that STAT1 could bind with sites 2/3 and 5/6 within human GLS1 promoter in IFN-α stimulated or HIV-1-infected monocyte-derived macrophages. Interestingly, we found that rat Gls1 promoter was regulated through a similar way as human GLS1 promoter. Together, our data identified critical elements that regulate GLS1 promoter activity.
PMCID: PMC3782442  PMID: 24086752
9.  miR-137, a new target for post-stroke depression? 
Neural Regeneration Research  2013;8(26):2441-2448.
Expression of miR-137 is downregulated in brain tissue from patients with depression and suicidal behavior, and is also downregulated in peripheral blood from stroke patients. However, it is not yet known if miR-137 acts as a bridge between stroke and depression. To test this, we used middle cerebral artery occlusion and chronic mild stress to establish a post-stroke depression model in rats. Compared with controls, we found significantly lower miR-137 levels in the brain and peripheral blood from post-stroke depression rats. Injection of a miR-137 antagonist into the brain ventricles upregulated miR-137 levels, and improved behavioral changes in post-stroke depression rats. Luciferase assays showed miR-137 bound to the 3’UTR of Grin2A, regulating Grin2A expression in a neuronal cell line. Grin2A gene overexpression in the brain of post-stroke depression rats, noticeably suppressed the inhibitory effect of miR-137 on post-stroke depression. Overall, our results show that miR-137 suppresses Grin2A protein expression through binding to Grin2A mRNA, thereby exerting an inhibitory effect on post-stroke depression. Our results offer a new therapeutic direction for post-stroke depression.
PMCID: PMC4146110  PMID: 25206554
neural regeneration; brain injury; post-stroke depression; microRNA; cerebrovascular disease; Grin2A; miR-137; neuroregeneration
10.  S-SAD phasing study of death receptor 6 and its solution conformation revealed by SAXS 
A comparative analysis of sulfur phasing of death receptor 6 (DR6) using data collected at wavelengths of 2.0 and 2.7 Å is presented. SAXS analysis of unliganded DR6 defines a dimer as the minimum physical unit in solution.
A subset of tumour necrosis factor receptor (TNFR) superfamily members contain death domains in their cytoplasmic tails. Death receptor 6 (DR6) is one such member and can trigger apoptosis upon the binding of a ligand by its cysteine-rich domains (CRDs). The crystal structure of the ectodomain (amino acids 1–348) of human death receptor 6 (DR6) encompassing the CRD region was phased using the anomalous signal from S atoms. In order to explore the feasibility of S-SAD phasing at longer wavelengths (beyond 2.5 Å), a comparative study was performed on data collected at wavelengths of 2.0 and 2.7 Å. In spite of sub-optimal experimental conditions, the 2.7 Å wavelength used for data collection showed potential for S-SAD phasing. The results showed that the R ano/R p.i.m. ratio is a good indicator for monitoring the anomalous data quality when the anomalous signal is relatively strong, while d′′/sig(d′′) calculated by SHELXC is a more sensitive and stable indicator applicable for grading a wider range of anomalous data qualities. The use of the ‘parameter-space screening method’ for S-SAD phasing resulted in solutions for data sets that failed during manual attempts. SAXS measurements on the ectodomain suggested that a dimer defines the minimal physical unit of an unliganded DR6 molecule in solution.
PMCID: PMC3335285  PMID: 22525750
sulfur phasing; SAXS analysis; long-wavelength X-rays; death receptor 6
11.  Methylenetetrahydrofolate Reductase Polymorphisms and Risk of Acute Lymphoblastic Leukemia-Evidence from an updated meta-analysis including 35 studies 
BMC Medical Genetics  2012;13:77.
5,10-methylenetetrahydrofolate reductase (MTHFR) variants, C677T and A1298C, have been reported to be associated with decreased risk of acute lymphoblastic leukemia (ALL). However, results derived from individually underpowered studies are conflicting. We carried out an updated meta-analysis on the association between MTHFR polymorphisms and ALL risk.
Relevant publications were searched through PUBMED and EMBASE databases. The associations between MTHFR C677T and A1298C polymorphisms and the risk of ALL were evaluated by odds ratios (ORs). The heterogeneity and publication bias were estimated. Meta-regression analysis was performed to evaluate the potential sources of heterogeneity.
C677T polymorphism was associated with a reduced risk of ALL (allele contrast: ORRE = 0.91, 95% CI: 0.83-0.99). Subgroup analysis showed MTHFR C677T variant was associated with decreased susceptibility to ALL in children and Caucasians. Meta-regression showed the logOR for the association between T allele and ALL increased as sex ratio (M/F) in the case group increased (P = 0.01). Regarding A1298C polymorphism, no significant association was observed (allele contrast: ORRE = 1.01, 95% CI: 0.91-1.11). There was no publication bias for C677T or A1298C polymorphism.
The present meta-analysis suggests that the C677T polymorphism, not A1298C, in MTHFR gene is associated with a decreased risk of ALL, particularly among children and Caucasians subjects. Our findings suggest that the influence of the C677T polymorphism on ALL susceptibility is modified by sex ratio in cases (M/F). Since folate intake may be a possible confounding factor, including this factor in future prospective studies is warranted. Further meta-analysis studies should be at least stratified for folate levels and gender to give more powerful and informative results.
PMCID: PMC3459788  PMID: 22943282
Acute lymphoblastic leukemia; Polymorphism; Meta-analysis; 5,10-methylenetetrahydrofolate reductase; Update
12.  Glutaminase dysregulation in HIV-1-infected human microglia mediates neurotoxicity: relevant to HIV-1 associated neurocognitive disorders 
Microglia represent the main cellular targets of HIV-1 in the brain. Infected and/or activated microglia play a pathogenic role in HIV-associated neurocognitive disorders (HAND) by instigating primary dysfunction and subsequent death of neurons. Although microglia are known to secrete neurotoxins when infected with HIV-1, the detailed mechanism of neurotoxicity remains unclear. Using a human microglia primary culture system and macrophage-tropic HIV-1 strains, we have now demonstrated that HIV-1 infection of microglia resulted in a significant increase in extracellular glutamate concentrations and elevated levels of neurotoxicity. RNA and protein analysis revealed upregulation of the glutamate-generating enzyme glutaminase isoform glutaminase C in HIV-1-infected microglia. The clinical relevance of these findings was further corroborated with investigation of post mortem brain tissues. The glutaminase C levels in the brain tissues of HIV dementia individuals were significantly higher than HIV serum negative control and correlated with elevated concentrations of glutamate. When glutaminase was subsequently inhibited by siRNA or by a small molecular inhibitor, the HIV-induced glutamate production and the neuronal loss was diminished. In conclusion, these findings support glutaminase as a potential component of the HAND pathogenic process as well as a novel therapeutic target in their treatment.
PMCID: PMC3407550  PMID: 22016553
HIV-1-associated dementia; microglia; glutamate; glutaminase; excitotoxicity
13.  Interferon-α Regulates Glutaminase 1 Promoter through STAT1 Phosphorylation: Relevance to HIV-1 Associated Neurocognitive Disorders 
PLoS ONE  2012;7(3):e32995.
HIV-1 associated neurocognitive disorders (HAND) develop during progressive HIV-1 infection and affect up to 50% of infected individuals. Activated microglia and macrophages are critical cell populations that are involved in the pathogenesis of HAND, which is specifically related to the production and release of various soluble neurotoxic factors including glutamate. In the central nervous system (CNS), glutamate is typically derived from glutamine by mitochondrial enzyme glutaminase. Our previous study has shown that glutaminase is upregulated in HIV-1 infected monocyte-derived-macrophages (MDM) and microglia. However, how HIV-1 leads to glutaminase upregulation, or how glutaminase expression is regulated in general, remains unclear. In this study, using a dual-luciferase reporter assay system, we demonstrated that interferon (IFN) α specifically activated the glutaminase 1 (GLS1) promoter. Furthermore, IFN-α treatment increased signal transducer and activator of transcription 1 (STAT1) phosphorylation and glutaminase mRNA and protein levels. IFN-α stimulation of GLS1 promoter activity correlated to STAT1 phosphorylation and was reduced by fludarabine, a chemical that inhibits STAT1 phosphorylation. Interestingly, STAT1 was found to directly bind to the GLS1 promoter in MDM, an effect that was dependent on STAT1 phosphorylation and significantly enhanced by IFN-α treatment. More importantly, HIV-1 infection increased STAT1 phosphorylation and STAT1 binding to the GLS1 promoter, which was associated with increased glutamate levels. The clinical relevance of these findings was further corroborated with investigation of post-mortem brain tissues. The glutaminase C (GAC, one isoform of GLS1) mRNA levels in HIV associated-dementia (HAD) individuals correlate with STAT1 (p<0.01), IFN-α (p<0.05) and IFN-β (p<0.01). Together, these data indicate that both HIV-1 infection and IFN-α treatment increase glutaminase expression through STAT1 phosphorylation and by binding to the GLS1 promoter. Since glutaminase is a potential component of elevated glutamate production during the pathogenesis of HAND, our data will help to identify additional therapeutic targets for the treatment of HAND.
PMCID: PMC3316554  PMID: 22479354
14.  UBE2W Interacts with FANCL and Regulates the Monoubiquitination of Fanconi Anemia Protein FANCD2 
Molecules and Cells  2011;31(2):113-122.
Fanconi anemia (FA) is a rare cancer-predisposing genetic disease mostly caused by improper regulation of the monoubiquitination of Fanconi anemia complementation group D2 (FANCD2). Genetic studies have indicated that ubiquitin conjugating enzyme UBE2T and HHR6 could regulate FANCD2 monoubiquitination through distinct mechanisms. However, the exact regulation mechanisms of FANCD2 monoubiquitination in response to different DNA damages remain unclear. Here we report that UBE2W, a new ubiquitin conjugating enzyme, could regulate FANCD2 monoubiquitination by mechanisms different from UBE2T or HHR6. Indeed, UBE2W exhibits ubiquitin conjugating enzyme activity and catalyzes the monoubiquitination of PHD domain of Fanconi anemia complementation group L (FANCL) in vitro. UBE2W binds to FANCL, and the PHD domain is both necessary and sufficient for this interaction in mammalian cells. In addition, overexpression of UBE2W in cells promotes the monoubiquitination of FANCD2 and down-regulated UBE2W markedly reduces the UV irradiation-induced but not MMC-induced FANCD2 monoubiquitination. These results indicate that UBE2W regulates FANCD2 monoubiquitination by mechanisms different from UBE2T and HRR6. It may provide an additional regulatory step in the activation of the FA pathway.
PMCID: PMC3932686  PMID: 21229326
DNA repair; FANCD2 monoubiquitination; FA pathway; FANCL; fanconi anemia; UBE2W
15.  The interaction between the PARP10 protein and the NS1 protein of H5N1 AIV and its effect on virus replication 
Virology Journal  2011;8:546.
During the process that AIV infect hosts, the NS1 protein can act on hosts, change corresponding signal pathways, promote the translation of virus proteins and result in virus replication.
In our study, we found that PARP domain and Glu-rich region of PARP10 interacted with NS1, and the presence of NS1 could induce PARP10 migrate from cytoplasm to nucleus. NS1 high expression could reduce the endogenous PARP10 expression. Cell cycle analysis showed that with inhibited PARP10 expression, NS1 could induce cell arrest in G2-M stage, and the percentage of cells in G2-M stage rise from the previous 10%-45%, consistent with the cell proliferation result. Plague forming unit measurement showed that inhibited PARP10 expression could help virus replication.
In a word, our results showed that NS1 acts on host cells and PARP10 plays a regulating role in virus replication.
PMCID: PMC3287249  PMID: 22176891
16.  Cytotoxic Activities of New Jadomycin Derivatives 
The Journal of antibiotics  2005;58(6):405-408.
Cytotoxic activities of jadomycin B and five new jadomycin derivatives against four cancer cell lines (HepG2, IM-9, IM-9/Bcl-2 and H460) were evaluated. Jadomycin S was most potent against HepG2, IM-9 and IM-9/Bcl-2 while jadomycin F was most potent against H460. Their potencies correlated with the degrees of apoptosis induced. Structure-activity-relationship analyses clearly demonstrate that the side chains of the oxazolone ring derived from the incorporated amino acids make a significant impact on biological activity. Therefore, jadomycin offers an ideal scaffold to manipulate structure and could be exploited to make many novel bioactive compounds with altered activities.
PMCID: PMC2881663  PMID: 16156517
jadomycin; derivative; Streptomyces venezuelae; cytotoxic
17.  Interaction of influenza virus NS1 protein with growth arrest-specific protein 8 
Virology Journal  2009;6:218.
NS1 protein is the only non-structural protein encoded by the influenza A virus, and it contributes significantly to disease pathogenesis by modulating many virus and host cell processes. A two-hybrid screen for proteins that interact with NS1 from influenza A yielded growth arrest-specific protein 8. Gas8 associated with NS1 in vitro and in vivo. Deletion analysis revealed that the N-terminal 260 amino acids of Gas8 were able to interact with NS1, and neither the RNA-binding domain nor the effector domain of NS1 was sufficient for the NS1 interaction. We also found that actin, myosin, and drebrin interact with Gas8. NS1 and β-actin proteins could be co-immunoprecipitated from extracts of transfected cells. Furthermore, actin and Gas8 co-localized at the plasma membrane. These results are discussed in relation to the possible functions of Gas8 protein and their relevance in influenza virus release.
PMCID: PMC2797798  PMID: 19995461
18.  QKI Binds MAP1B mRNA and Enhances MAP1B Expression during Oligodendrocyte Development 
Molecular Biology of the Cell  2006;17(10):4179-4186.
Microtubule-associated protein 1B (MAP1B) is essential for neural development. Besides the abundant expression in neurons, MAP1B recently was found in myelinating oligodendroglia. Moreover, MAP1B deficiency causes delayed myelin development, suggesting the functional importance of MAP1B in oligodendroglia. However, molecular mechanisms that control MAP1B expression in oligodendroglia remain elusive. We report here that MAP1B mRNA is markedly up-regulated in the oligodendroglia cell line CG4 upon induced differentiation, leading to elevated MAP1B protein production. A coordinated regulation of homeoprotein transcription factors was observed during CG4 cell differentiation, which recapitulates the regulation in neurons that promotes MAP1B transcription. Hence, transcriptional regulation of MAP1B appears to be a common mechanism in both neurons and oligodendroglia. In addition, we found posttranscriptional regulation of MAP1B mRNA by the selective RNA-binding protein QKI in oligodendroglia. The 3′UTR of MAP1B mRNA interacts with QKI, and oligodendroglia-specific QKI-deficiency in the quakingviable mutant mice resulted in reduced MAP1B mRNA expression. Moreover, RNAi-mediated QKI-knockdown caused destabilization of the MAP1B mRNA in CG4 cells. Furthermore, forced expression of exogenous QKI was sufficient for promoting MAP1B expression. Because QKI is absent in neurons, QKI-dependent stabilization of MAP1B mRNA provides a novel mechanism for advancing MAP1B expression specifically in oligodendroglia during brain development.
PMCID: PMC1635361  PMID: 16855020

Results 1-18 (18)