bluuebunny/crossref_metadata_2025_split huggingface dataset:
Repression of MAL tumour suppressor activity by promoter methylation during cervical carcinogenesis
Authors: Overmeer Renée M , Henken Florianne E , Bierkens Mariska , Wilting Saskia M , Timmerman Ilse , Meijer Chris JLM , Snijders Peter JF , Steenbergen Renske DM 
Published: July 2009

AbstractWe recently identified MAL (T‐lymphocyte maturation associated protein) as the most down‐regulated gene in cervical oncogenesis. Here, we examined the mechanism underlying MAL silencing, its functional role in cervical carcinogenesis, and the relevance of detecting MAL alterations for risk assessment of hrHPV‐positive women. MAL mRNA expression and promoter methylation were analysed in primary keratinocytes, hrHPV‐immortalized keratinocytes, cervical cancer cell lines, biopsies, and scrapings by quantitative (methylation‐specific) PCR. SiHa cells were transfected with MAL cDNA and assayed for proliferation, migration, and anchorage‐independent growth. MAL mRNA was (nearly) undetectable in all HPV‐immortalized and cervical cancer cells, but could be up‐regulated upon methylation inhibition. MAL promoter methylation at two promoter regions (M1 and M2) was detected in all HPV‐immortalized cells and cancer cells. Ectopic expression of MAL in SiHa cells suppressed proliferation, migration, and anchorage‐independent growth. None (0/22) of normal cervical biopsies, 9% (6/66) of CIN1 lesions, 53% (34/64) of CIN3 lesions, 90% (85/94) of cervical squamous cell carcinomas (SCCs), and 93% (26/28) of cervical adenocarcinomas (AdCAs) demonstrated MAL promoter methylation at both promoter regions. Moreover, detection of MAL promoter methylation in cervical scrapings was predictive for underlying high‐grade lesions. Both in biopsies and in scrapings, MAL promoter methylation was significantly correlated with reduced mRNA expression. MAL gene silencing by promoter methylation is a frequent and biologically essential event in HPV‐induced cervical carcinogenesis. Hence, MAL promoter methylation and/or mRNA expression analysis on cervical scrapings may provide a valuable diagnostic tool to improve the detection of CIN3, SCC, and AdCA. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Conditional deletion of the Lkb1 gene in the mouse mammary gland induces tumour formation
Authors: McCarthy Afshan , Lord Christopher J , Savage Kay , Grigoriadis Anita , Smith Darrin P , Weigelt Britta , Reis‐Filho Jorge S , Ashworth Alan 
Published: July 2009

AbstractHeterozygous germline mutations in the LKB1 (STK11) gene cause Peutz‐Jeghers syndrome (PJS), an autosomal dominant disorder characterized by hamartomatous polyposis of the gastrointestinal tract and an increased risk of colorectal, breast, and other cancers. To model the role of LKB1 mutation in mammary tumourigenesis, we have used a conditional gene targeting strategy to generate a mouse in which exons encoding the kinase domain of Lkb1 were deleted specifically in the mammary gland. Mammary gland tumours developed in these mice with a latency of 46–85 weeks and occurred in the thoracic or inguinal glands. These tumours were grade 2 invasive ductal carcinomas or solid papillary carcinomas with histological features similar to those described in breast cancers arising in patients with PJS. This mouse model of Lkb1 deficiency provides a potentially useful tool to investigate the role of Lkb1 in tumourigenesis and to guide the development of therapeutic approaches. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The transcriptional regulatory function of p53 is essential for suppression of mouse skin carcinogenesis and can be dissociated from effects on TGF‐β‐mediated growth regulation
Authors: Ponnamperuma Roshini M , King Kathryn E , Elsir Tamador , Glick Adam B , Wahl Geoffrey M , Nister Monica , Weinberg Wendy C 
Published: July 2009

AbstractTranscriptional regulation by p53 is critical for p53‐mediated tumour suppression; however, p53‐mediated transactivation has been dissociated from p53‐mediated biological processes including apoptosis, DNA repair, and differentiation. We compared the effects of a mutant allele, p53QS − val135, containing a double mutation in the amino‐terminus abrogating transactivation activity and a modification at amino acid 135 partially affecting DNA binding, to complete loss of p53. We applied in vitro endpoints correlated with epithelial tumourigenesis and an in vivo assay of tumour phenotype to assess whether loss of p53‐mediated transcriptional regulation underlies the malignant phenotype of p53−/−/v‐rasHa‐overexpressing keratinocytes. Transactivation deficiency of p53QS‐val135 was confirmed by reporter gene assays in fibroblasts and differentiating keratinocytes. Ras oncogene‐induced senescence was lost in both p53QS − val135/QS − val135 and p53−/− keratinocytes. Similarly, p53QS − val135/QS − val135, like p53−/−, cooperated with v‐rasHa to enhance malignant conversion. The tumours arising in p53QS − val135/QS − val135 keratinocytes displayed strong nuclear p53 expression; thus, the p53QS − val135 allele was maintained and the deficient transactivation function of the expressed p53QS mutant protein was supported by absence of p21waf1 in these tumours. The p53QS − val135 allele did not confer a dominant‐negative phenotype, as p53+/QS − val135 keratinocytes senesced normally in response to v‐rasHa expression and formed benign tumours. While p53−/− keratinocytes displayed diminished response to TGF‐β, p53QS − val135/QS − val135 and p53+/+ keratinocytes responded equivalently, indicating that the requirement for p53 in maximizing TGF‐β‐mediated growth regulation is independent of its transactivation domain and that the ability of keratinocytes to respond to TGF‐β is insufficient to suppress the malignant phenotype in this model. Furthermore, TGF‐β enhances p53QS‐induced activation of a dual p53‐TGF‐β responsive reporter in a keratinocyte cell line. These findings support an essential role for p53‐mediated transcriptional regulation in suppressing malignancies arising from ras‐induced skin tumours, consistent with previous findings in spontaneous carcinogenesis in other organs, and highlight the potential importance of senescence for tumour suppression in vivo. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Central nervous system medication use and incident mobility limitation in community elders: the health, aging, and body composition study
Authors: Boudreau Robert M. , Hanlon Joseph T. , Roumani Yazan F. , Studenski Stephanie A. , Ruby Christine M. , Wright Rollin M. , Hilmer Sarah N. , Shorr Ronald I. , Bauer Douglas C. , Simonsick Eleanor M. , Newman Anne B. 
Published: July 2009

AbstractPurposeTo evaluate whether CNS medication use in older adults was associated with a higher risk of future incident mobility limitation.MethodsThis 5‐year longitudinal cohort study included 3055 participants from the health, aging and body composition (Health ABC) study who were well‐functioning at baseline. CNS medication use (benzodiazepine and opioid receptor agonists, antipsychotics, and antidepressants) was determined yearly (except year 4) during in‐home or in‐clinic interviews. Summated standardized daily doses (low, medium, and high) and duration of CNS drug use were computed. Incident mobility limitation was operationalized as two consecutive self‐reports of having any difficulty walking 1/4 mile or climbing 10 steps without resting every 6 months after baseline. Multivariable Cox proportional hazard analyses were conducted adjusting for demographics, health behaviors, health status, and common indications for CNS medications.ResultsEach year at least 13.9% of participants used a CNS medication. By year 6, overall 49% had developed incident mobility limitation. In multivariable models, CNS medication users compared to never users showed a higher risk for incident mobility limitation (adjusted hazard ratio (Adj. HR) 1.28; 95% confidence interval (CI) 1.12–1.47). Similar findings of increased risk were seen in analyses examining dose– and duration–response relationships.ConclusionsCNS medication use is independently associated with an increased risk of future incident mobility limitation in community dwelling elderly. Further studies are needed to determine the impact of reducing CNS medication exposure on mobility problems. Copyright © 2009 John Wiley & Sons, Ltd.
Copolymerization of norbornene and 5‐norbornene‐2‐yl acetate using novel bis(β‐ketonaphthylamino)Ni(II)/B(C6F5)3/AlEt3 catalytic system
Authors: He Fuping , Chen Yiwang , He Xiaohui , Chen Muqing , Zhou Weihua , Wu Qing 
Published: July 2009

AbstractVinyl‐type copolymerization of norbornene (NBE) and 5‐NBE‐2‐yl‐acetate (NBE‐OCOMe) in toluene were investigated using a novel homogeneous catalyst system based on bis(β‐ketonaphthylamino)Ni(II)/B(C6F5)3/AlEt3. The copolymerization behavior as well as the copolymerization conditions, such as the levels of B(C6F5)3 and AlEt3, temperature, and monomer feed ratios, which influence on the copolymerization were examined. Without combination of AlEt3, the catalytic bis(β‐ketonaphthylamino)Ni(II)/B(C6F5)3 exhibited very high catalyst activity for polymerization of NBE. Combination of AlEt3 in catalyst system resulted in low conversion for polymerization of NBE. For copolymerization of NBE and NBE‐OCOMe, involvement of AlEt3 in catalyst is necessary. Slight addition of NBE‐OCOMe in copolymerization of NBE and NBE‐OCOMe gives rise to significant increase of catalyst activity for catalytic system bis(β‐ketonaphthylamino)Ni(II)/B(C6F5)3/AlEt3. Nevertheless, excess increase of the NBE‐OCOMe content in the comonomer feed ratios results in decrease of conversion as well as activity of catalyst. The achieved copolymers were confirmed to be vinyl‐addition copolymers through the analysis of FTIR, 1H NMR, and 13C NMR spectra. 13C NMR studies further revealed the composition of the copolymer and the incorporation rate was 7.6–54.1 mol % ester units at a content of 30–90 mol % of the NBE‐OCOMe in the monomer feeds ratios. TGA analysis results showed that the copolymer exhibited good thermal stability (Td > 410 °C) and failed to observe the glass transitions temperature over 300 °C. The copolymers are confirmed to be noncrystalline by WAXD analysis results and show good solubility in common organic solvents. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 3990–4000, 2009
Competing stoichiometric phases and the intermediate phase in GexSe1−x glasses
Authors: Inam F. , Tafen D. N. , Chen Gang , Drabold D. A. 
Published: July 2009

AbstractRaman and calorimetric studies on GexSe1−x glasses have provided evidence for the existence of the intermediate phase (IP) in chalcogenide and other glasses. Ab initio molecular dynamics models of these glasses are discussed, and an atomistic picture of the IP, based upon the models and available experiments is presented. Analysis of our models reveals that the IP in GexSe1−x glasses may arise from the competition between amorphous GeSe2 and a polymeric a‐Se phase, which gives rise to the non‐monotonic evolution of the network parameters through the IP window. A possible electronic signature of the IP in terms of the shift in the conduction edge in the IP range is also observed.
Resistivity of boron doped diamond
Authors: Barjon J. , Habka N. , Mer C. , Jomard F. , Chevallier J. , Bergonzo P. 
Published: July 2009

AbstractIn this Letter, we present a significant advance in boron‐doped diamond material synthesis, with film resistivities reduced by almost two orders of magnitude with respect to the reference data of the field for boron concentrations in the range from 1 × 1018 to 3 × 1019 cm–3. The study is conducted on a series of boron‐doped diamond homoepitaxial layers grown using the microwave plasma assisted vapour phase epitaxy. The electrical properties were obtained from Hall effect measurements and conductivity data probed in the van der Paw configuration at room temperature. This work highlights the important progress made on diamond material synthesis over the last decade, with significant advances in the reduction of compensation effects. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Genotoxicity and antigenotoxicity evaluation of non‐photoactivated hypericin
Authors: Miadokova Eva , Chalupa Ivan , Vlckova Viera , Sevcovicova Andrea , Nadova Slavomira , Kopaskova Marcela , Hercegova Alena , Gasperova Patricia , Alfoldiova Lubica , Komjatiova Monika , Csanyiova Zuzana , Galova Eliska , Cellarova Eva , Vlcek Daniel 
Published: July 2009

AbstractThe potential genotoxicity and antigenotoxicity of non‐photoactivated hypericin was investigated in five experimental models. Hypericin was non‐mutagenic in the Ames assay, with and without metabolic activation. It did not exert a protective effect against mutagenicity induced by 9‐aminoacridine. In a yeast (Saccharomyces cerevisiae) assay, hypericin did not increase the frequency of mitotic crossovers or total aberrants at theade2locus, the number of convertants at thetrp5locus, or the number of revertants at theilv1locus. In combined application with 4‐nitroquinoline‐1‐oxide, it significantly enhanced the number of revertants at theilv1locus at the highest concentration used. Hypericin was not mutagenic in the algaChlamydomonas reinhardtii. However, in combined application with methyl methane sulfonate, toxicity and mutagenicity were slightly reduced. In a chromosome aberration assay using three mammalian cell lines, hypericin did not alter the frequency of structural chromosome aberrations, and in the DPPH radical scavenging assay, it did not exert any antioxidant effects. Copyright © 2009 John Wiley & Sons, Ltd.
Cytochrome P450 2C19 inhibitory activity of common berry constituents
Authors: Sand Philipp G. , Dreiseitel Andrea , Stang Martin , Schreier Peter , Oehme Anett , Locher Sanja , Hajak Goeran 
Published: July 2009

AbstractThe cytochrome P450 enzyme CYP2C19 is involved in the metabolism of many commonly prescribed drugs, including proton pump inhibitors, antiepileptics and antidepressants. CYP2C19 inhibitors from food and food supplements may augment the toxicity of these agents and lead to noncompliance with treatment. The present investigation addresses CYP2C19 inhibition by 18 berry constituents using a chemiluminescent assay. Test compounds displayed inhibitory properties in a concentration‐dependent fashion, with IC50values ranging from 20.2 µMup to >316 µM. In the order of decreasing effect size, anthocyanidins were followed by anthocyanidin‐monoglycosides and procyanidins. Anthocyanidin‐diglucosides exhibited weak and biphasic effects. When compared with the CYP2C19 inhibitor fluvoxamine, the flavonoids under study were 50‐ to 750‐fold less potent. It is concluded that the above natural substances are moderate to poor inhibitors of CYP2C19in vitro. Copyright © 2009 John Wiley & Sons, Ltd.
Kaempferol and quercetin, components of Ginkgo biloba extract (EGb 761), induce caspase‐3‐dependent apoptosis in oral cavity cancer cells
Authors: Kang Ju Wan , Kim Jeong Hong , Song Keejae , Kim Si Hong , Yoon Joo‐Heon , Kim Kyung‐Su 
Published: July 2009

AbstractEGb 761, extracted from Ginkgo biloba leaves, has been proven to induce caspase‐3‐dependent apoptosis in oral cavity cancer cells. Since EGb 761 is a composition of various components, it is important to identify which components are responsible for its anticancer effects to reduce the total dosage and to avoid toxicity. Therefore, the study aimed to determine the effective compounds of EGb 761 that induce apoptosis in oral cavity cancer cells and to identify whether caspase‐3 was involved in apoptosis of oral cancer cells by EGb 761 components. The results of cell proliferation assays on oral cavity cancer cells showed that kaempferol and quercetin significantly inhibited cellular proliferation at a concentration of 40 µM. Flow cytometry showed that the antiproliferative effects of each component were due to increased apoptosis. Kaempferol and quercetin induced apoptosis in various oral cancer cell lines (SCC‐1483, SCC‐25 and SCC‐QLL1) and showed cleavage of poly (ADP‐ribose) polymerase (PARP). Caspase‐3 activity assay revealed that induction of apoptosis by kaempferol and quercetin was caspase‐3‐dependent. In conclusion, the results suggest that kaempferol and quercetin, two components of EGb 761, effectively induce caspase‐3‐dependent apoptosis of oral cavity cancer cells and can be considered as possible anti‐oral cavity cancer agents. Copyright © 2009 John Wiley & Sons, Ltd.
Efficacy of purslane in the treatment of oral lichen planus
Authors: Agha‐Hosseini Farzaneh , Borhan‐Mojabi Katayun , Monsef‐Esfahani Hamid‐Reza , Mirzaii‐Dizgah Iraj , Etemad‐Moghadam Shahroo , Karagah Aida 
Published: July 2009

AbstractThis study evaluated the effectiveness of antioxidant‐rich purslane in the treatment of oral lichen planus (OLP). A total of 37 biopsy‐proven symptomatic OLP patients were selected for this randomized double‐blind placebo‐controlled trial. All subjects were divided into two groups to receive purslane (n = 20) or placebo (n = 17) for 3 months. Assessments were made at baseline, after 2 weeks and each month for 6 months, based on the visual analog scale (VAS) and clinical improvement including lesion type and size. Approximately 83% of the purslane patients showed partial to complete clinical improvement but 17% had no response. In the placebo group 17% experienced partial improvement, 73% did not respond and 10% showed worsening. According to VAS scores, a partial to complete response was observed in all purslane‐treated patients, while 71%, 15% and 14% of the controls demonstrated partial response, no response and worsening of the symptoms, respectively. A significant decrease in VAS scores was seen at the end of the study period (p < 0.001). No serious side‐effects occurred in either of the groups. According to our findings purslane is clinically effective in the treatment of OLP. Considering the lack of side‐effects during the study period, it may be a favorable alternative treatment for OLP. Copyright © 2009 John Wiley & Sons, Ltd.
Protective effect of Morinda citrifolia fruits on β‐amyloid (25–35) induced cognitive dysfunction in mice: An experimental and biochemical study
Authors: Muralidharan P. , Kumar V. Ravi , Balamurugan G. 
Published: July 2009

AbstractThe neuroprotective effect of an ethyl acetate extract of Morinda citrifolia (Rubiaceae) Linn. fruits (EMC, ethyl acetate extract of Morinda citrifolia) at doses of 200 and 400 mg/kg, p.o. was studied on β‐amyloid (25–35) peptide induced cognitive dysfunction in mice. In the step‐down inhibitory avoidance, EMC exhibited a significant increase in short‐term memory and long‐term memory (p < 0.05). A significant decrease (p < 0.01) in escape latency was noticed in the animals in the water maze. A significant increase (p < 0.01) in alteration of behavior was exhibited upon administration of EMC 200 and 400 mg/kg on the Y maze. Exploratory parameters such as line crossings, head dipping and rearing were increased significantly in EMC treated groups in a dose‐dependent manner (p < 0.05 and p < 0.01). A significant reduction (p < 0.05) in acetyl cholinesterase activity was noticed in the EMC 200 and 400 mg/kg treated groups. The level of monoamine oxidase‐A was decreased by the administration of EMC 200 and 400 mg/kg (p < 0.05 and p < 0.01, respectively). EMC at a dose of 400 mg/kg exhibited a significant increase (p < 0.01) in the levels of serotonin and dopamine. Antioxidant enzymes such as superoxide dismutase, glutathione reductase, glutathione peroxidase and ascorbic acid were decreased significantly in the b‐amyloid peptide injected group, whose levels were restored significantly (p < 0.01) by the administration of EMC (400 mg/kg). Copyright © 2009 John Wiley & Sons, Ltd.
Radiographic evidence of mandibular osteoporosis improvement in Wistar rats treated with Ginkgo biloba
Authors: Lucinda Leda Marília Fonseca , Toledo de Oliveira Tânia , Salvador Pollyanna Amaral , Peters Vera Maria , Reis João Evangelista de Paula , Guerra Martha de Oliveira 
Published: July 2009

AbstractObjective: Evaluate the effects of the extract of Ginkgo biloba (EGb) on the rat mandibular glucocorticoid‐induced‐osteoporosis. Method: 36 female rats were divided into six groups (n=6): control, osteoporosis, positive control and EGb1 (14mg/kg/day), EGb2 (28mg/kg/day), and EGb3 (56mg/kg/day) treatment. Treatments were conducted for 30 days after osteoporosis induction. The animals were euthanized and their left mandibles were removed and radiographed to evaluate the cortical and the periodontal bone support. The control group was compared with the osteoporosis group (Student's t‐test). The other groups were analyzed by ANOVA test followed by Tukey post‐hoc test (p < 0.05). Results: There was a significant reduction in periodontal bone support in the osteoporosis group. The positive control group showed a significant increase in the mesial periodontal bone support, as well as the EGb group treated with 28 and 56 mg/Kg, which showed a significant increase in the mesial and distal periodontal bone support. The mandibular cortical was not affected by osteoporosis; however, the group treated with EGb using 56 mg/Kg showed a significant increase in the thickness of the mandibular cortical. Conclusions: The EGb recovered the periodontal bone support and increased the mandibular cortical thickness. The EGb may be effective in the treatment of osteoporosis. Copyright © 2009 John Wiley & Sons, Ltd.
Objective filtering of ensemble‐based background‐error variances
Authors: Raynaud Laure , Berre Loïk , Desroziers Gérald 
Published: July 2009

AbstractFlow‐dependent background‐error variances can be estimated by means of an ensemble of assimilations. However, the finite size of the ensemble implies a sampling noise, which is detrimental for the variance estimation. This article presents a filtering procedure for ensemble‐estimated variance fields, which relies on an estimate of spectral signal/noise ratios.It is first demonstrated that the sampling noise covariance can be expressed analytically as a simple function of the background‐error covariance. The resulting formula shows in particular that the spatial structure of the sampling noise is closely related to the spatial structure of background error (i.e. to its correlation function). It is then explained how this relation can be used to calculate an objective filter.Investigations are first conducted in a highly idealized 1D framework, to show that the proposed filter is able to remove most of the sampling noise, while extracting the signal of interest. Application to an ensemble of Météo‐France Arpège forecasts is then considered. This objective filter reveals a vertical‐level dependence, with a larger signal/noise ratio near the surface, and a scale separation between signal and noise which is more pronounced in altitude. The results also indicate that, after applying such an optimized filter, variance estimates obtained from a six‐member ensemble have a residual estimation error variance around 10%.Some insights are then given into the spatio‐temporal dynamics of the variance field. It is observed that the globally averaged background‐error variance is fairly stable in time, while spatial patterns of the variance field are closely linked to the meteorological situation, with high values found in the vicinity of troughs.Finally, impact studies in the Arpège system show that the filtering of vorticity variances has a positive impact on the quality of the NWP system. Copyright © 2009 Royal Meteorological Society