PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-25 (43)
 

Clipboard (0)
None

Select a Filter Below

Year of Publication
more »
1.  Evaluation of GWAS-identified genetic variants for age at menarche among Chinese women 
Human Reproduction (Oxford, England)  2013;28(4):1135-1143.
STUDY QUESTION
Do genetic polymorphisms which influence age at menarche in women of European ancestry also influence women of Chinese ancestry?
SUMMARY ANSWER
Many genetic variants influencing age at menarche in European populations appear to impact Chinese populations in a similar manner.
WHAT IS KNOWN AND WHAT THIS PAPER ADDS
Prior genome-wide association studies have uncovered 42 SNPs associated with age at menarche in European populations. This study is the first to demonstrate that many of the genetic determinants of age at menarche are shared between European and Chinese women.
PARTICIPANTS AND SETTING
We evaluated 37 of 42 SNPs identified as associated with age at menarche from a recent, large meta-analysis, consisting primarily of women of European ancestry, in a population of 6929 Chinese women from Shanghai, China. We also constructed weighted genetic risk scores (GRSs) combining the number of effect variants for all 37 SNPs, or only the SNPs associated with age at menarche among our study population, to evaluate their joint influence on age at menarche.
MAIN RESULTS
For 32 of the 37 evaluated variants, the direction of the allele associations were the same between women of European ancestry and women of Chinese ancestry (P = 3.71 × 10−6, binomial sign test); 9 of these were statistically significant. Subjects in the highest quintile of GRSs began menarche ∼5 months later than those in the lowest quintile.
BIAS, LIMITATIONS AND GENERALIZABILITY TO OTHER POPULATIONS
Age at menarche was obtained by self-report, which can be subject to recall errors. The current analysis was restricted to loci which met or approached GWAS significance thresholds and did not evaluate loci which may act predominantly or exclusively in the Chinese population. The smaller sample size for our meta-analysis compared with meta-analyses conducted in European populations reduced the power to detect significant results.
STUDY FUNDING/COMPETING INTERESTS
This study was supported, in part, by grants from US National Institutes of Health (grants R01CA124558, R01CA090899, R01CA070867; R01CA064277 and R01CA092585 and UL1 RR024975), Ingram professorship funds and Allen Foundation funds. There are no competing interests to declare.
doi:10.1093/humrep/det011
PMCID: PMC3600840  PMID: 23406970
menarche; genome-wide association study; genetics; reproductive endocrinology
2.  Anorexic effects of intra-VTA leptin are similar in low-fat and high-fat-fed rats but attenuated in a subgroup of high-fat-fed obese rats 
Leptin is an adiposity hormone that plays an important role in regulating food intake and energy homeostasis. This study investigated the effects of a high-fat (HF) and a low-fat, high-carbohydrate/sugar (LF) diet on leptin sensitivity in the ventral tegmental area (VTA) in rats. The animals were exposed to a HF or LF diet for 16 weeks. Then the effects of intra-VTA leptin (150 and 500 ng/side, unilateral dose) on food intake and body weights were investigated while the animals were maintained on the HF or LF diet. Long-term exposure to the HF or LF diet led to similar body weight gain in these groups. The HF-fed animals consumed a smaller amount of food by weight than the LF-fed animals but both groups consumed the same amount of calories. The bilateral administration of leptin into the VTA decreased food intake (72 h) and body weights (48 h) to a similar degree in the HF and LF-fed animals. When the HF-fed animals were ranked by body weight gain it was shown that the diet-induced obese rats (HF-fed DIO, upper quartile for weight gain) were less sensitive to the effects of leptin on food intake and body weights than the diet-resistant rats (HF-fed DR, lower quartile for weight gain). A control experiment with fluorescent Cy3-labeled leptin showed that leptin did not spread beyond the borders of the VTA. This study indicates that leptin sensitivity in the VTA is the same in animals that are exposed to a HF or LF diet. However, HF-fed DIO rats are less sensitive to the effects of leptin in the VTA than HF-fed DR rats. Leptin resistance in the VTA might contribute to overeating and weight gain when exposed to a HF diet.
doi:10.1016/j.pbb.2012.10.012
PMCID: PMC3545044  PMID: 23107643
Leptin; Cy3-leptin; ventral tegmental area; food intake; high-fat diet; diet-induced obese; rats
3.  The Increase of the Functional Entropy of the Human Brain with Age 
Scientific Reports  2013;3:2853.
We use entropy to characterize intrinsic ageing properties of the human brain. Analysis of fMRI data from a large dataset of individuals, using resting state BOLD signals, demonstrated that a functional entropy associated with brain activity increases with age. During an average lifespan, the entropy, which was calculated from a population of individuals, increased by approximately 0.1 bits, due to correlations in BOLD activity becoming more widely distributed. We attribute this to the number of excitatory neurons and the excitatory conductance decreasing with age. Incorporating these properties into a computational model leads to quantitatively similar results to the fMRI data. Our dataset involved males and females and we found significant differences between them. The entropy of males at birth was lower than that of females. However, the entropies of the two sexes increase at different rates, and intersect at approximately 50 years; after this age, males have a larger entropy.
doi:10.1038/srep02853
PMCID: PMC3793229  PMID: 24103922
4.  Cathepsin H Functions as an Aminopeptidase in Secretory Vesicles for Production of Enkephalin and Galanin Peptide Neurotransmitters 
Journal of neurochemistry  2012;122(3):512-522.
Peptide neurotransmitters function as key intercellular signaling molecules in the nervous system. These peptides are generated in secretory vesicles from proneuropeptides by proteolytic processing at dibasic residues, followed by removal of N- and/or C-terminal basic residues to form active peptides. Enkephalin biosynthesis from proenkephalin utilizes the cysteine protease cathepsin L and the subtilisin-like prohormone convertase 2 (PC2). Cathepsin L generates peptide intermediates with N-terminal basic residue extensions, which must be removed by an aminopeptidase. In this study, we identified cathepsin H as an aminopeptidase in secretory vesicles that produces (Met)enkephalin (ME) by sequential removal of basic residues from KR-ME and KK-ME, supported by in vivo knockout of the cathepsin H gene. Localization of cathepsin H in secretory vesicles was demonstrated by immunoelectron microscopy and confocal immunofluorescence microscopy. Purified human cathepsin H sequentially removes N-terminal basic residues to generate ME, with peptide products characterized by nano-LC-MS/MS tandem mass spectrometry. Cathepsin H shows highest activities for cleaving N-terminal basic residues (Arg and Lys) among amino acid fluorogenic substrates. Notably, knockout of the cathepsin H gene results in reduction of ME in mouse brain. Cathepsin H deficient mice also show a substantial decrease in galanin peptide neurotransmitter levels in brain. These results illustrate a role for cathepsin H as an aminopeptidase for enkephalin and galanin peptide neurotransmitter production.
doi:10.1111/j.1471-4159.2012.07788.x
PMCID: PMC3417130  PMID: 22582844
aminopeptidase; cathepsin H; peptide neurotransmitter; enkephalin; galanin; secretory vesicle; neuropeptide; protease
5.  miR-375 is upregulated in acquired paclitaxel resistance in cervical cancer 
Shen, Y | Wang, P | Li, Y | Ye, F | Wang, F | Wan, X | Cheng, X | Lu, W | Xie, X
British Journal of Cancer  2013;109(1):92-99.
Background:
Chemo-resistance is one of the key causal factors in cancer death and emerging evidences suggest that microRNAs (miRNAs) have critical roles in the regulation of chemo-sensitivity in cancers. Cervical cancer is one of the most common malignancies in women and insensitive to chemotherapy clinically.
Methods:
The differentially expressed miRNAs in cervical squamous cell carcinoma tissues were screened by using a microarray platform (μParaflo Sanger miRBase release 13.0). The expression of miR-375 was determined by stem-loop RT–PCR using 23 clinical cervical cancer samples and 2 cervical cancer cell lines. We exogenously upregulated miR-375 expression in SiHa and Caski cells using a pre-miRNA lentiviral vector transfection and observed its impact on paclitaxel sensitivity using MTS. The cells that stably overexpressed miR-375 were subcutaneously injected into mice to determine tumour growth and chemo-sensitivity in vivo.
Results:
Twenty-one differentially expressed miRNAs were found by miRNA microarray between pro- and post-paclitaxel cervical cancer tissues. Of those, miR-375 showed consistent high expression levels across paclitaxel-treated cervical cells and tissues. Paclitaxel induced upregulated miR-375 expression in a clear dose-dependent manner. Forced overexpression of miR-375 in cervical cancer cells decreased paclitaxel sensitivity in vitro and in vivo.
Conclusion:
Collectively, our results suggest that miR-375 might be a therapeutic target in paclitaxel-resistant cervical cancer.
doi:10.1038/bjc.2013.308
PMCID: PMC3708577  PMID: 23778521
miR-375; paclitaxel; chemo-resistance; cervical cancer
6.  Studies of TBX4 and chromosome 17q23.1q23.2: an uncommon cause of nonsyndromic clubfoot 
Clubfoot is a common birth defect characterized by inward posturing and rigid downward displacement of one or both feet. The etiology of syndromic forms of clubfoot is varied and the causes of isolated clubfoot are not well understood. A microduplication of 2.2 Mb on chromosome 17q23.1q23.2 which includes T-box 4 (TBX4), a hindlimb-specific gene, and 16 other genes was recently identified in 3 of 66 families reported as nonsyndromic clubfoot, but additional non-foot malformations place them in the syndromic clubfoot category. Our study assesses whether variation in or around TBX4 contributes to nonsyndromic clubfoot. To determine whether this microduplication was a common cause of nonsyndromic clubfoot, 605 probands (from 148 multiplex and 457 simplex families) with nonsyndromic clubfoot were evaluated by copy number and oligonucleotide array CGH testing modalities. Only one multiplex family (0.68%) that had 16 with clubfoot and 9 with other foot anomalies, had a 350kb microduplication, which included the complete duplication of TBX4 and NACA2 and partial duplication of BRIP1. The microduplication was transmitted in an autosomal dominant pattern and all with the microduplication had a range of phenotypes from short wide feet and toes to bilateral clubfoot. Minimal evidence was found for an association between TBX4 and clubfoot and no pathogenic sequence variants were identified in the two known TBX4 hindlimb enhancer elements. Altogether, these results demonstrate that variation in and around the TBX4 gene and the 17q23.1q23.2 microduplication are not a frequent cause of this common orthopedic birth defect and narrows the 17q23.1q23.2 nonsyndromic clubfoot-associated region.
doi:10.1002/ajmg.a.35418
PMCID: PMC3381434  PMID: 22678995
Clubfoot; genetics; TBX4; microduplication; association; malformation
9.  ZNF143 transcription factor mediates cell survival through upregulation of the GPX1 activity in the mitochondrial respiratory dysfunction 
Cell Death & Disease  2012;3(11):e422-.
Mitochondrial respiratory dysfunction has intimate relationship with redox regulation. The key mechanism about how the mitochondrial respiration-defective cells survive oxidative stress is still elusive. Here, we report that transcription factor zinc-finger protein 143 (ZNF143) expression and glutathione peroxidase (GPX) activity are markedly increased in the mitochondrial respiratory-defective cells induced by dominant-negative DNA polymerase γ (POLGdn). In this work, investigation of the cellular antioxidant glutathione (GSH) and enzyme GPX activity in the mitochondrial dysfunction revealed the presence of an increased synthesis of GSH through the activation of GCLC (glutamate–cysteine ligase catalytic subunit) and GCLM (glutamate–cysteine ligase regulatory subunit) gene expression, and also a positive upregulation of glutathione peroxidase 1 (GPX1) activity by the transcription factor ZNF143. Significant increase in gene expression of SepSecS, the key enzyme responsible for selenocysteine transfer RNA (tRNA) synthesis, further confirmed the activation of the selenocysteine synthesis pathway. By using both GPX1 and ZNF143 knockdown, we provided insight into the involvement of ZNF143 in promoting GPX1 activity and protecting cells from oxidative damage and cisplatin treatment in the mitochondrial dysfunction. Furthermore, we reported the possible regulation of mitochondrial transcription factor A (TFAM) in the mitochondrial dysfunction. Our findings delineate an important antioxidant survival pathway that allows the mitochondrial-defective cells to survive oxidative stress and cisplatin treatment.
doi:10.1038/cddis.2012.156
PMCID: PMC3542592  PMID: 23152058
ZNF143; mitochondrial dysfunction; GPX1; cisplatin; ROS
10.  Effects of insulin and leptin in the ventral tegmental area and arcuate hypothalamic nucleus on food intake and brain reward function in female rats 
Behavioural brain research  2011;219(2):254-264.
There is evidence for a role of insulin and leptin in food intake, but the effects of these adiposity signals on the brain reward system are not well understood. Furthermore, the effects of insulin and leptin on food intake in females are underinvestigated. These studies investigated the role of insulin and leptin in the ventral tegmental area (VTA) and the arcuate hypothalamic nucleus (Arc) on food intake and brain reward function in female rats. The intracranial self-stimulation procedure was used to assess the effects of insulin and leptin on the reward system. Elevations in brain reward thresholds are indicative of a decrease in brain reward function. The bilateral administration of leptin into the VTA (15–500 ng/side) or Arc (15–150 ng/side) decreased food intake for 72 h. The infusion of leptin into the VTA or Arc resulted in weight loss during the first 48 (VTA) or 24 h (Arc) after the infusions. The administration of insulin (0.005–5 mU/side) into the VTA or Arc decreased food intake for 24 h but did not affect body weights. The bilateral administration of low, but not high, doses of leptin (15 ng/side) or insulin (0.005 mU/side) into the VTA elevated brain reward thresholds. Neither insulin nor leptin in the Arc affected brain reward thresholds. These studies suggest that a small increase in leptin or insulin levels in the VTA leads to a decrease in brain reward function. A relatively large increase in insulin or leptin levels in the VTA or Arc decreases food intake.
doi:10.1016/j.bbr.2011.01.020
PMCID: PMC3062744  PMID: 21255613
leptin; insulin; food; reward; arcuate nucleus; ventral tegmental area
11.  Mortalin–p53 interaction in cancer cells is stress dependent and constitutes a selective target for cancer therapy 
Cell Death and Differentiation  2011;18(6):1046-1056.
Stress protein mortalin is a multifunctional protein and is highly expressed in cancers. It has been shown to interact with tumor suppressor protein-p53 (both wild and mutant types) and inactivates its transcriptional activation and apoptotic functions in cancer cells. In the present study, we found that, unlike most of the cancer cells, HepG2 hepatoma lacked mortalin–p53 interaction. We demonstrate that the mortalin–p53 interaction exists in cancer cells that are either physiologically stressed (frequently associated with p53 mutations) or treated with stress-inducing chemicals. Targeting mortalin–p53 interaction with either mortalin small hairpin RNA or a chemical or peptide inhibitor could induce p53-mediated tumor cell-specific apoptosis in hepatocellular carcinoma; p53-null hepatoma or normal hepatocytes remain unaffected.
doi:10.1038/cdd.2010.177
PMCID: PMC3131943  PMID: 21233847
stress; mortalin–p53 interaction; cancer; target; therapy
12.  Association of genetic variation in FTO with risk of obesity and type 2 diabetes with data from 96,551 East and South Asians 
Diabetologia  2011;55(4):981-995.
Aims/hypothesis
FTO harbours the strongest known obesity-susceptibility locus in Europeans. While there is growing evidence for a role for FTO in obesity risk in Asians, its association with type 2 diabetes, independently of BMI, remains inconsistent. To test whether there is an association of the FTO locus with obesity and type 2 diabetes, we conducted a meta-analysis of 32 populations including 96,551 East and South Asians.
Methods
All studies published on the association between FTO-rs9939609 (or proxy [r2 > 0.98]) and BMI, obesity or type 2 diabetes in East or South Asians were invited. Each study group analysed their data according to a standardised analysis plan. Association with type 2 diabetes was also adjusted for BMI. Random-effects meta-analyses were performed to pool all effect sizes.
Results
The FTO-rs9939609 minor allele increased risk of obesity by 1.25-fold/allele (p = 9.0 × 10−19), overweight by 1.13-fold/allele (p = 1.0 × 10−11) and type 2 diabetes by 1.15-fold/allele (p = 5.5 × 10−8). The association with type 2 diabetes was attenuated after adjustment for BMI (OR 1.10-fold/allele, p = 6.6 × 10−5). The FTO-rs9939609 minor allele increased BMI by 0.26 kg/m2 per allele (p = 2.8 × 10−17), WHR by 0.003/allele (p = 1.2 × 10−6), and body fat percentage by 0.31%/allele (p = 0.0005). Associations were similar using dominant models. While the minor allele is less common in East Asians (12–20%) than South Asians (30–33%), the effect of FTO variation on obesity-related traits and type 2 diabetes was similar in the two populations.
Conclusions/interpretation
FTO is associated with increased risk of obesity and type 2 diabetes, with effect sizes similar in East and South Asians and similar to those observed in Europeans. Furthermore, FTO is also associated with type 2 diabetes independently of BMI.
Electronic supplementary material
The online version of this article (doi:10.1007/s00125-011-2370-7) contains peer-reviewed but unedited supplementary material, which is available to authorised users.
doi:10.1007/s00125-011-2370-7
PMCID: PMC3296006  PMID: 22109280
Asians; FTO; Meta-analysis; Obesity; Type 2 diabetes
13.  Prediction of RNA-Binding Proteins by Voting Systems 
It is important to identify which proteins can interact with RNA for the purpose of protein annotation, since interactions between RNA and proteins influence the structure of the ribosome and play important roles in gene expression. This paper tries to identify proteins that can interact with RNA using voting systems. Firstly through Weka, 34 learning algorithms are chosen for investigation. Then simple majority voting system (SMVS) is used for the prediction of RNA-binding proteins, achieving average ACC (overall prediction accuracy) value of 79.72% and MCC (Matthew's correlation coefficient) value of 59.77% for the independent testing dataset. Then mRMR (minimum redundancy maximum relevance) strategy is used, which is transferred into algorithm selection. In addition, the MCC value of each classifier is assigned to be the weight of the classifier's vote. As a result, best average MCC values are attained when 22 algorithms are selected and integrated through weighted votes, which are 64.70% for the independent testing dataset, and ACC value is 82.04% at this moment.
doi:10.1155/2011/506205
PMCID: PMC3149752  PMID: 21826121
14.  Strontium borate glass: potential biomaterial for bone regeneration 
Boron plays important roles in many life processes including embryogenesis, bone growth and maintenance, immune function and psychomotor skills. Thus, the delivery of boron by the degradation of borate glass is of special interest in biomedical applications. However, the cytotoxicity of borate glass which arises with the rapid release of boron has to be carefully considered. In this study, it was found that the incorporation of strontium into borate glass can not only moderate the rapid release of boron, but also induce the adhesion of osteoblast-like cells, SaOS-2, thus significantly increasing the cyto-compatibility of borate glass. The formation of multilayers of apatite with porous structure indicates that complete degradation is optimistic, and the spread of SaOS-2 covered by apatite to form a sandwich structure may induce bone-like tissue formation at earlier stages. Therefore, such novel strontium-incorporated borosilicate may act as a new generation of biomaterial for bone regeneration, which not only renders boron as a nutritious element for bone health, but also delivers strontium to stimulate formation of new bones.
doi:10.1098/rsif.2009.0504
PMCID: PMC2880081  PMID: 20031984
borate glass; strontium; cytotoxicity; bone regeneration
15.  Cyclic-di-GMP-Mediated Repression of Swarming Motility by Pseudomonas aeruginosa: the pilY1 Gene and Its Impact on Surface-Associated Behaviors▿  
Journal of Bacteriology  2010;192(12):2950-2964.
The intracellular signaling molecule cyclic-di-GMP (c-di-GMP) has been shown to influence surface-associated behaviors of Pseudomonas aeruginosa, including biofilm formation and swarming motility. Previously, we reported a role for the bifA gene in the inverse regulation of biofilm formation and swarming motility. The bifA gene encodes a c-di-GMP-degrading phosphodiesterase (PDE), and the ΔbifA mutant exhibits increased cellular pools of c-di-GMP, forms hyperbiofilms, and is unable to swarm. In this study, we isolated suppressors of the ΔbifA swarming defect. Strains with mutations in the pilY1 gene, but not in the pilin subunit pilA gene, show robust suppression of the swarming defect of the ΔbifA mutant, as well as its hyperbiofilm phenotype. Despite the ability of the pilY1 mutation to suppress all the c-di-GMP-related phenotypes, the global pools of c-di-GMP are not detectably altered in the ΔbifA ΔpilY1 mutant relative to the ΔbifA single mutant. We also show that enhanced expression of the pilY1 gene inhibits swarming motility, and we identify residues in the putative VWA domain of PilY1 that are important for this phenotype. Furthermore, swarming repression by PilY1 specifically requires the diguanylate cyclase (DGC) SadC, and epistasis analysis indicates that PilY1 functions upstream of SadC. Our data indicate that PilY1 participates in multiple surface behaviors of P. aeruginosa, and we propose that PilY1 may act via regulation of SadC DGC activity but independently of altering global c-di-GMP levels.
doi:10.1128/JB.01642-09
PMCID: PMC2901681  PMID: 20233936
16.  Gene silencing of HPV16 E6/E7 induced by promoter-targeting siRNA in SiHa cells 
Hong, D | Lu, W | Ye, F | Hu, Y | Xie, X
British Journal of Cancer  2009;101(10):1798-1804.
Background:
Recently, transcriptional gene silencing induced by small interfering RNA (siRNA) was found in mammalian and human cells. However, previous studies focused on endogenous genes.
Methods:
In this study, we designed siRNA targeting the promoter of human papillomavirus 16 E6/E7 and transfected it into the cervical cancer cell line, SiHa. E6 and E7 mRNA and protein expression were detected in cells treated by promoter-targeting siRNA. Futhermore, cellular growth, proliferation, apoptosis and senescence were detected. Thereafter, we investigated promoter DNA methylation and histone methylation status in cells treated with promoter-targeting siRNA.
Results:
We found that E6/E7 mRNA and protein were simultaneously reduced, cell growth and proliferation were inhibited and cell death, especially senescence, was remarkably increased. Meanwhile, we also found a significantly increasing histone H3-Lys9 methylation on the promoter when E6/E7 gene expression was inhibited.
Interpretation:
Our findings suggest that promoter-targeting siRNA effectively and simultaneously knocks down both extraneous HPV 16 E6 and E7 at the transcriptional level, and consequently inhibits proliferation and induces death in HPV 16-infected cells. This transcriptional repression is probably induced by histone modification rather than by alteration of DNA methylation.
doi:10.1038/sj.bjc.6605344
PMCID: PMC2778536  PMID: 19826423
small interfering RNA (siRNA); human papillomavirus (HPV); transcriptional gene silencing (TGS); senescence; histone methylation
17.  Solid-State NMR Studies of Chemically Lithiated CFx 
Journal of the Electrochemical Society  2010;157(2):A148-A154.
Three types of fluorinated carbon, all in their original form and upon sequential chemical lithiations via n-butyllithium, were investigated by 13C and 19F solid-state NMR methods. The three starting CFx materials [where x = 1 (nominally)] were fiber based, graphite based, and petroleum coke based. The aim of the current study was to identify, at the atomic/molecular structural level, factors that might account for differences in electrochemical performance among the different kinds of CFx. Differences were noted in the covalent F character among the starting compounds and in the details of LiF production among the lithiated samples.
PMCID: PMC2911803  PMID: 20676233
18.  Wnt signaling activation and mammary gland hyperplasia in MMTV-LRP6 transgenic mice: implication for breast cancer tumorigenesis 
Zhang, J | Li, Y | Liu, Q | Lu, W | Bu, G
Oncogene  2009;29(4):539-549.
Although Wnt signaling activation is frequently observed in human breast cancer, mutations in the genes encoding intracellular components of the Wnt signaling pathway are rare. We found that expression of Wnt signaling co-receptor LRP6 is up-regulated in a subset of human breast cancer tissues and cell lines. To examine whether overexpression of LRP6 in mammary epithelial cells is sufficient to activate Wnt signaling and promote cell proliferation, we generated transgenic mice overexpressing LRP6 in mammary epithelial cells driven by the mouse mammary tumor virus (MMTV) promoter. We found that mammary glands from MMTV-LRP6 mice exhibit significant Wnt activation evidenced by the translocation of β-catenin from membrane to cytoplasmic/nuclear fractions. Expression of several Wnt-target genes including Axin2, Cyclin D1 and c-Myc was also increased in MMTV-LRP6 mice. More importantly, mammary glands from virgin MMTV-LRP6 mice exhibit significant hyperplasia, a precursor to breast cancer, when compared to wild-type littermate controls. Several matrix metalloproteinases are up-regulated in MMTV-LRP6 mice that could contribute to the hyperplasia phenotype. Our results suggest that Wnt signaling activation at the cell surface receptor level can contribute to breast cancer tumorigenesis.
doi:10.1038/onc.2009.339
PMCID: PMC2813429  PMID: 19881541
LRP6; Wnt signaling; mammary gland; breast cancer
19.  Electronic Structures of S-Doped Capped C-SWNT from First Principles Study 
Nanoscale Research Letters  2010;5(6):1027-1031.
The semiconducting single-walled carbon nanotube (C-SWNT) has been synthesized by S-doping, and they have extensive potential application in electronic devices. We investigated the electronic structures of S-doped capped (5, 5) C-SWNT with different doping position using first principles calculations. It is found that the electronic structures influence strongly on the workfunction without and with external electric field. It is considered that the extended wave functions at the sidewall of the tube favor for the emission properties. With the S-doping into the C-SWNT, the HOMO and LUMO charges distribution is mainly more localized at the sidewall of the tube and the presence of the unsaturated dangling bond, which are believed to enhance workfunction. When external electric field is applied, the coupled states with mixture of localized and extended states are presented at the cap, which provide the lower workfunction. In addition, the wave functions close to the cap have flowed to the cap as coupled states and to the sidewall of the tube mainly as extended states, which results in the larger workfunction. It is concluded that the S-doped C-SWNT is not incentive to be applied in field emitter fabrication. The results are also helpful to understand and interpret the application in other electronic devices.
doi:10.1007/s11671-010-9594-1
PMCID: PMC2894202  PMID: 20672070
Single-walled carbon nanotube (C-SWNT); Electronic properties; Workfunctions
20.  Electronic Structures of S-Doped Capped C-SWNT from First Principles Study 
Nanoscale Research Letters  2010;5(6):1027-1031.
The semiconducting single-walled carbon nanotube (C-SWNT) has been synthesized by S-doping, and they have extensive potential application in electronic devices. We investigated the electronic structures of S-doped capped (5, 5) C-SWNT with different doping position using first principles calculations. It is found that the electronic structures influence strongly on the workfunction without and with external electric field. It is considered that the extended wave functions at the sidewall of the tube favor for the emission properties. With the S-doping into the C-SWNT, the HOMO and LUMO charges distribution is mainly more localized at the sidewall of the tube and the presence of the unsaturated dangling bond, which are believed to enhance workfunction. When external electric field is applied, the coupled states with mixture of localized and extended states are presented at the cap, which provide the lower workfunction. In addition, the wave functions close to the cap have flowed to the cap as coupled states and to the sidewall of the tube mainly as extended states, which results in the larger workfunction. It is concluded that the S-doped C-SWNT is not incentive to be applied in field emitter fabrication. The results are also helpful to understand and interpret the application in other electronic devices.
doi:10.1007/s11671-010-9594-1
PMCID: PMC2894202  PMID: 20672070
Single-walled carbon nanotube (C-SWNT); Electronic properties; Workfunctions
21.  Suitable Reference Gene Selection for Different Strains and Developmental Stages of the Carmine Spider Mite, Tetranychus cinnabarinus, using Quantitative Real-Time PCR 
Sun, W. | Jin, Y. | He, L | Lu, W-C. | Li, M.
Reference genes are used as internal controls in gene expression studies, but their expression levels vary according to tissue types and experimental treatments. Quantitative real-time PCR (qPCR) is the most sensitive technique for transcript quantification provided that gene transcription patterns are normalized to an evaluated reference gene. In this study, the suitability of eight commonly used genes (β?-actin, 5.8SrRNA, α?-TUB, GAPDH, RPL13a, RPS18, TBP, SDHA) were cloned and investigated to find the most stable candidates for normalizing real-time PCR data generated from the four different strains (abamectin-resistant, fenpropathrin-resistant, omethoate-resistant, and susceptible strains) and different developmental stages (eggs, protonymphs, nymphs, and adults) of carmine spider mite, Tetranychus cinnabarinus (Boisduval) (Acarina: Tetranychidae). The stability of gene expression was assessed using two different analysis programs, geNorm and NormFinder. Using these analyses, RPS18 and 5.8SrRNA had the most stable expression regardless of the four different strains, whereas RPS18 and α?-TUB were expressed most stably in different developmental stages.
doi:10.1673/031.010.20801
PMCID: PMC3029232  PMID: 21265619
normalization
22.  Loss of PKD1 and loss of Bcl-2 elicit polycystic kidney disease through distinct mechanisms 
Cell death and differentiation  2005;13(7):1123-1127.
We have recently demonstrated that ablation of one or both alleles of the proapoptotic gene Bim prevents the polycystic kidney disease (PKD) that develops in mice deficient for the prosurvival protein Bcl-2. The aim of the present study was to investigate whether loss of Bim or Bcl-2 could influence the disease in the PKD1del34/del34 mutant mice, a model of autosomal dominant PKD. PKD1del34/del34 mice were intercrossed with Bim-deficient mice and Bcl-2+/− mice to generate double mutants. Loss of Bim does not prevent the development of PKD in PKD1del34/del34 mice. On the C57BL/6 genetic background, most older PKD1del34/+ mice do not develop PKD, but present with liver cysts. Surprisingly, loss of Bim completely prevented liver cysts formation in PKD1del34/+ mice. Loss of one Bcl-2 allele did not influence the PKD1del34 phenotype significantly. We conclude that loss of PKD1 and loss of Bcl-2 elicit PKD through distinct mechanisms.
doi:10.1038/sj.cdd.4401815
PMCID: PMC2795698  PMID: 16282979
Polycystic kidney disease; Bcl-2; PKD1; Bim; apoptosis
24.  Dynamics of the Trimeric AcrB Transporter Protein Inferred From a B-Factor Analysis of the Crystal Structure 
Proteins  2006;62(1):152-158.
The Escherichia coli AcrB multi-drug transporter recognizes a wide range of toxic chemicals and actively extrudes them from cells. The molecular basis of multidrug transport in AcrB remains unknown. Herein, we describe normal mode analyses to study important regions for drug recognition and extrusion in this transporter. Based on the X-ray structure of AcrB, an elastic network model has been able to correct errors arising from crystal imperfection in the experimental B-factors. The results allow us to understand the functional dynamics of this membrane protein. It is expected that this technique can be applied to other membrane proteins with known structures.
doi:10.1002/prot.20743
PMCID: PMC2705243  PMID: 16288462
multidrug transporter; efflux pump; B-factors; anisotropic network model (ANM); normal mode analysis; membrane protein
25.  A Fuzzy Reasoning Design for Fault Detection and Diagnosis of a Computer-Controlled System 
A Fuzzy Reasoning and Verification Petri Nets (FRVPNs) model is established for an error detection and diagnosis mechanism (EDDM) applied to a complex fault-tolerant PC-controlled system. The inference accuracy can be improved through the hierarchical design of a two-level fuzzy rule decision tree (FRDT) and a Petri nets (PNs) technique to transform the fuzzy rule into the FRVPNs model. Several simulation examples of the assumed failure events were carried out by using the FRVPNs and the Mamdani fuzzy method with MATLAB tools. The reasoning performance of the developed FRVPNs was verified by comparing the inference outcome to that of the Mamdani method. Both methods result in the same conclusions. Thus, the present study demonstratrates that the proposed FRVPNs model is able to achieve the purpose of reasoning, and furthermore, determining of the failure event of the monitored application program.
doi:10.1016/j.engappai.2007.04.007
PMCID: PMC2598772  PMID: 19255619
Error detection; Error diagnosis; Petri nets; Fuzzy rule

Results 1-25 (43)