bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Activation of MEK/ERK Signaling Pathway by Bone Morphogenetic Protein 4 to Increase Hepatocellular Carcinoma Cell Proliferation and Migration
Authors: Chiu Chiang-Yen , Kuo Kung-Kai , Kuo Tzu-Lei , Lee King-The , Cheng Kuang-Hung 
Published: January 2012

AbstractHepatocellular carcinoma (HCC) is one of the most common visceral malignancies worldwide, with a very high incidence and poor prognosis. Bone morphogenesis protein 4 (BMP4), which belongs to the TGF-β superfamily of proteins, is a multifunctional cytokine, which exerts its biologic effects through SMAD- and non-SMAD-dependent pathways, and is also known to be involved in human carcinogenesis. However, the effects of the BMP4 signaling in liver carcinogenesis are not yet clearly defined. Here, we first show that BMP4 and its receptor, BMPR1A, are overexpressed in a majority of primary HCCs and that it promotes the growth and migration of HCC cell lines in vitro. We also establish that BMP4 can induce HCC cyclin-dependent kinase (CDK)1 and cyclin B1 upregulation to accelerate cell-cycle progression. Our study indicates that the induction of HCC cell proliferation is independent of the SMAD signaling pathway, as Smad4 knockdown of HCC cell lines still leads to the upregulation of CDK1 and cyclin B1 expression after BMP4 treatment. Using mitogen-activated protein/extracellular signal-regulated kinase (MEK) selective inhibitors, the induction of CDK1, cyclin B1 mRNA and protein were shown to be dependent on the activation of MEK/extracellular signal-regulated kinase (ERK) signaling. In vivo xenograft studies confirmed that the BMPR1A-knockdown cells were significantly less tumorigenic than the control groups. Our findings show that the upregulation of BMP4 and BMPR1A in HCC promotes the proliferation and metastasis of HCC cells and that CDK1 and cyclin B1 are important SMAD-independent molecular targets in BMP4 signaling pathways, during the HCC tumorigenesis. It is proposed that BMP4 signaling pathways may have potential as new therapeutic targets in HCC treatment. Mol Cancer Res; 10(3); 415–27. ©2012 AACR.
Phosphoinositide 3-kinase/AKT/mTORC1/2 Signaling Determines Sensitivity of Burkitt's Lymphoma Cells to BH3 mimetics
Authors: Spender Lindsay C. , Inman Gareth J. 
Published: January 2012

Abstract
Burkitt's lymphoma (BL), driven by translocation and overexpression of the c-MYC gene, is an aggressive, highly proliferative lymphoma, and novel therapeutic strategies are required to overcome drug resistance following conventional treatments. The importance of the prosurvival BCL-2 family member BCL-XL in BL cell survival suggests that antagonistic BH3-mimetic compounds may have therapeutic potential. Here, we show that treatment of BL cell lines with ABT-737 induces caspase-3/7 activation and apoptosis with varying potency. Using selective inhibitors, we identify phosphoinositide 3-kinase (PI3K) as a proproliferative/survival pathway in BL cells and investigate the potential of combined pharmacologic inhibition of both the BCL-2 family and PI3K signaling pathway. PI3K/AKT inhibition and ABT-737 treatment induced synergistic caspase activation, augmented BL cell apoptosis, and rendered chemoresistant cells sensitive. Targeting mTORC1/2 with PP242 was also effective, either as a monotherapy or, more generally, in combination with ABT-737. The combined use of a dual specificity PI3K/mTOR inhibitor (PI 103) with ABT-737 proved highly efficacious. PI 103 treatment of BL cells was associated with an increase in BIM/MCL-1 expression ratios and loss of c-MYC expression. Furthermore, blocking c-MYC function using the inhibitor 10058-F4 also induced apoptosis synergistically with ABT-737, suggesting that maintenance of expression of BCL-2 family members and/or c-MYC by the PI3K/AKT/mTOR pathway could contribute to BL cell survival and resistance to ABT-737. The combined use of BH3 mimetics and selective mTORC1/2 inhibitors may therefore be a useful novel therapeutic approach for the treatment of B-cell malignancy, including chemoresistant lymphomas. Mol Cancer Res; 10(3); 347–59. ©2012 AACR.
Nrf3-Pla2g7 Interaction Plays an Essential Role in Smooth Muscle Differentiation From Stem Cells
Authors: Xiao Qingzhong , Pepe Anna E. , Wang Gang , Luo Zhenling , Zhang Li , Zeng Lingfang , Zhang Zhongyi , Hu Yanhua , Ye Shu , Xu Qingbo 
Published: January 2012

Objective—

Phospholipase A
2
, group 7 (Pla2g7) is an important mediator in cardiovascular development and diseases because of its divergent physiological and pathological functions in inflammation and oxidative stress. However, little is known about the functional role of Pla2g7 in smooth muscle cell (SMC) differentiation from stem cells.

Methods and Results—
In the present study, embryonic stem cells were cultivated on collagen IV-coated plates to allow SMC differentiation. Pla2g7 gene expression and activity were upregulated significantly following 4 to 14 days of cell differentiation and colocalized with SMC differentiation markers in the differentiated SMCs. Knockdown of Pla2g7 resulted in downregulation of smooth muscle–specific markers in vitro and impairment of SMC differentiation in vivo, whereas enforced expression of Pla2g7 enhanced SMC differentiation and increased reactive oxygen species generation. Importantly, enforced expression of Pla2g7 significantly increased the binding of serum response factor to SMC differentiation gene promoters, resulting in SMC differentiation, which was abolished by free radical scavenger and flavoprotein inhibitor of NADPH oxidase but not hydrogen peroxide inhibitor. Moreover, we demonstrated that nuclear factor erythroid 2-related factor 3 (Nrf3) regulates Pla2g7 gene expression through direct binding to the promoter regions of Pla2g7 gene.

Conclusion—
Our findings demonstrated that Pla2g7 plays a crucial physiological role in SMC differentiation from stem cells, and the fine interactions between Nrf3 and Pla2g7 are essential for SMC differentiation.
Metabolic Syndrome in Adolescence
Authors: Efstathiou Stamatis P. , Skeva Irini I. , Zorbala Evi , Georgiou Evangelos , Mountokalakis Theodore D. 
Published: January 2012

Background—
There are well-established predisposing factors for the development of metabolic syndrome (MetS) in childhood or adolescence, but no specific risk profile has been identified as yet. The Prediction of Metabolic Syndrome in Adolescence (PREMA) study was conducted (1) to construct a classification score that could detect children at high risk for MetS in adolescence and (2) to test its predictive accuracy.

Methods and Results—

In the derivation cohort (1270 children), data from natal and parental profile and from initial laboratory assessment at 6 to 8 years of age were used to detect independent predictors of MetS at 13 to 15 years of age according to the International Diabetes Federation definition. In the validation cohort (1091 adolescents), the discriminatory capacity of the derived prediction score was tested on an independent adolescent population. MetS was diagnosed in 105 adolescents in the derivation phase (8%), whereas birth weight <10th percentile (odds ratio, 6.02; 95% confidence interval, 2.53–10.12,
P
<0.001), birth head circumference <10th percentile (odds ratio, 4.15; 95% confidence interval, 2.04–7.14,
P
<0.001), and parental overweight or obesity (in at least 1 parent; odds ratio, 3.22; 95% confidence interval, 1.30–5.29,
P
<0.01) were independently associated with diagnosis of MetS in adolescence. Among adolescents in the validation cohort (86 [8%] with MetS), the presence of all these 3 predictors predicted MetS with a sensitivity of 91% and a specificity of 98%.

Conclusions—
The coexistence of low birth weight, small head circumference, and parental history of overweight or obesity may be useful for detection of children at risk of developing MetS in adolescence.
On the North Atlantic Ocean Heat Content Change between 1955–70 and 1980–95
Authors: Zhai Xiaoming , Sheldon Luke 
Published: January 2012

Abstract
The upper-ocean heat content of the North Atlantic has undergone significant changes over the last 50 years but the underlying physical mechanisms are not yet well understood. In the present study, the authors examine the North Atlantic ocean heat content change in the upper 700 m between the 1955–70 and 1980–95 periods. Consistent with previous studies, the large-scale pattern consists of warming of the tropics and subtropics and cooling of the subpolar ocean. However, this study finds that the most significant heat content change in the North Atlantic during these two time periods is the warming of the Gulf Stream region. Numerical experiments strongly suggest that this warming in the Gulf Stream region is largely driven by changes of the large-scale wind forcing. Furthermore, the increased ocean heat content in the Gulf Stream region appears to feedback on to the atmosphere, resulting in warmer surface air temperature and enhanced precipitation there.
ENSO’s Impact on the Gap Wind Regions of the Eastern Tropical Pacific Ocean*
Authors: Alexander Michael A. , Seo Hyodae , Xie Shang Ping , Scott James D. 
Published: January 2012

Abstract
The recently released NCEP Climate Forecast System Reanalysis (CFSR) is used to examine the response to ENSO in the northeast tropical Pacific Ocean (NETP) during 1979–2009. The normally cool Pacific sea surface temperatures (SSTs) associated with wind jets through the gaps in the Central American mountains at Tehuantepec, Papagayo, and Panama are substantially warmer (colder) than the surrounding ocean during El Niño (La Niña) events. Ocean dynamics generate the ENSO-related SST anomalies in the gap wind regions as the surface fluxes damp the SSTs anomalies, while the Ekman heat transport is generally in quadrature with the anomalies. The ENSO-driven warming is associated with large-scale deepening of the thermocline; with the cold thermocline water at greater depths during El Niño in the NETP, it is less likely to be vertically mixed to the surface, particularly in the gap wind regions where the thermocline is normally very close to the surface. The thermocline deepening is enhanced to the south of the Costa Rica Dome in the Papagayo region, which contributes to the local ENSO-driven SST anomalies. The NETP thermocline changes are due to coastal Kelvin waves that initiate westward-propagating Rossby waves, and possibly ocean eddies, rather than by local Ekman pumping. These findings were confirmed with regional ocean model experiments: only integrations that included interannually varying ocean boundary conditions were able to simulate the thermocline deepening and localized warming in the NETP during El Niño events; the simulation with variable surface fluxes, but boundary conditions that repeated the seasonal cycle, did not.
Propagation of Kuroshio Extension Meanders between 143° and 149°E
Authors: Tracey Karen L. , Watts D. Randolph , Donohue Kathleen A. , Ichikawa Hiroshi 
Published: January 2012

Abstract
A two-dimensional array of current- and pressure-recording inverted echo sounders provided synoptic measurements of the upper and deep fluctuations in the Kuroshio Extension between 143° and 149°E with mesoscale resolution. Downstream-propagating meanders with periods of 3–60 days were always present between June 2004 and September 2005. Propagation speeds were estimated by two methods: spectral analysis of path displacements and complex empirical orthogonal functions (CEOF) analysis of along-path anomalies. The two methods produced similar results. Phase speeds increased smoothly from 10 km day−1 (0.12 m s−1) for meanders with wavelengths and periods [λ, T] = [420 km, 40 days] to 35 km day−1 (0.41 m s−1) for [λ, T] = [220 km, 6 days] meanders. This empirically derived dispersion relationship is indistinguishable from that obtained for Gulf Stream meanders downstream of Cape Hatteras. The deep ocean was populated with remotely generated, upstream-propagating eddies composed of a nearly depth-independent current structure. Upper meanders and deep eddies jointly spun up when they encountered each other with the deep eddy offset about a quarter wavelength ahead of the upper meander. Subsequently, as the upper and deep features moved past each other and the vertical offset changed, intensification ceased.
Prevalence of Biofilms and Their Response to Medical Treatment in Chronic Rhinosinusitis without Polyps
Authors: Tatar Emel Çadallı , Tatar İlkan , Öcal Bülent , Korkmaz Hakan , Saylam Güleser , Özdek Ali , Çelik Hakan Hamdi 
Published: January 2012

ObjectiveThe aim of this study was to investigate the prevalence of biofilms and the effects of medical treatment modalities in chronic rhinosinusitis (CRS) patients without nasal polyps.Study DesignRandomized controlled trial.SettingsTertiary referral hospital.Subjects and MethodsThe authors randomly divided 32 adult patients with CRS without nasal polyps into 2 groups. In the first group (n = 16), oral clarithromycin was administered 500 mg/bid for 2 weeks and then 250 mg/d for the following 6 weeks. In the second group (n = 16), an 8‐week course of 200‐mcg/d topical mometasone furoate was added to the clarithromycin regimen, identical to the first group. The pre‐ and posttreatment nasal tissue samples were evaluated by scanning electron microscopy for biofilm prevalence and graded from 0 to 3 according to density and extension.ResultsBiofilms were detected in 24 of 32 patients (75%) before the treatment (grades 1‐3). Biofilms were detected in 14 of 32 patients (43.8%) after the treatment (grades 1‐2). When each group was evaluated independently, there was a significant improvement after the treatment in both groups I and II. When the biofilm grades of group I were compared to those of group II, there was no significant difference both in the pre‐ and posttreatment evaluation.ConclusionThe prevalence of biofilms in CRS without polyps was 75% in our study. Regression of biofilms to 43% was observed under medical treatment. Adding nasal steroids to macrolides gave no further benefit.
Vertical Incision Intraoral Silicone Chin Augmentation
Authors: Aynehchi Behrad B. , Burstein David H. , Parhiscar Afshin , Erlich Mark A. 
Published: January 2012

ObjectiveSolid silicone augmentation mentoplasty is a common procedure with consistent aesthetic results in properly selected patients. While many plastic surgeons employ the external approach, the intraoral method affords excellent aesthetic outcomes while avoiding an external scar. This is the largest series in the literature describing the midline intraoral incision approach with minimal disruption of soft tissues.Study DesignCase series.SettingAcademic medical center.Subjects and MethodsOne hundred twenty‐five patients underwent chin augmentation with solid silicone implants between 2004 and 2010. Among these implants, 105 were placed transorally. Eighty‐five patients were followed for at least 1 year. Demographic information, indications, patient satisfaction questionnaire results, and complications were recorded.ResultsAll implants yielded satisfactory results with no displacement, infection, tissue reaction, lower lip incompetence, mental nerve injury, or intraoral implant contamination. Two cases of superficial mucosal irritation at the suture site were observed and resolved without consequence. Symmetry, projection, and overall balance of facial components were excellent. Although all patients were satisfied with the functional and aesthetic results, 20% stated they would like further augmentation. Patients were extremely satisfied with the lack of an external scar.ConclusionsBased on our series, the intraoral technique with a midline incision avoiding disruption of the mentalis muscle is recommended for its ease, simplicity, patient satisfaction, low complication rate, and circumvention of an external scar. The external approach should be considered in cases that require a very large implant.
Effectiveness of Personalized and Interactive Health Risk Calculators
Authors: Harle Christopher A. , Downs Julie S. , Padman Rema 
Published: January 2012

Background Risk calculators are popular websites that provide individualized disease risk assessments to the public. Little is known about their effect on risk perceptions and health behavior. Objective This study sought to test whether risk calculator features—namely, personalized estimates of one’s disease risk and feedback about the effects of risk-mitigating behaviors—improve risk perceptions and motivate healthy behavior. Design A web-based experimental study using simple randomization was conducted to compare the effects of 3 prediabetes risk communication websites. Setting The study was conducted in the context of ongoing health promotion activities sponsored by a university’s human resources office. Patients Participants were adult university employees. Intervention The control website presented nonindividualized risk information. The personalized noninteractive website presented individualized risk calculations. The personalized interactive website presented individualized risk calculations and feedback about the effects of hypothetical risk-mitigating behaviors. Measurements Pre- and postintervention risk perceptions were measured in absolute and relative terms. Health behavior was measured by assessing participant interest in follow-up preventive health services. Results On average, risk perceptions decreased by 2%. There was no general effect of personalization or interactivity in aligning subjective risk perceptions with objective risk calculations or in increasing healthy behaviors. However, participants who previously overestimated their risk reduced their perceptions by 16%. This was a significantly larger change than the 2% increase by participants who underestimated their risk. Limitations Results may not generalize to different populations, different diseases, or longer-term outcomes. Conclusions Compared to nonpersonalized information, individualized risk calculators had little positive effect on prediabetes risk perception accuracy or health behavior. Risk perception accuracy was improved in people who receive relatively “good news” about risk rather than “bad news.”
History and clinical use of thoracoscopy/pleuroscopy in respiratory medicine
Authors: Loddenkemper R. , Mathur P.N. , Lee P. , Noppen M. 
Published: January 2012

SummaryThoracoscopy was introduced over 100 years ago and for 40 years has been mainly used in the pneumothorax treatment of tuberculosis in those cases where pleuro-pulmonary adhesions prevented collapse of the lung. In the 1950s, the pneumothorax treatment of tuberculosis came to an end and thoracoscopy was used in a few centres by chest physicians as a diagnostic and therapeutic method in several pleuro-pulmonary diseases. In the 1990s, thoracic surgeons introduced the technique for minimally invasive surgery, known as “surgical thoracoscopy” or more precisely “video-assisted thoracic surgery” (VATS), which is performed under general anaesthesia with one-lung ventilation. In contrast, medical thoracoscopy/pleuroscopy can be performed under local anaesthesia or conscious sedation, in an endoscopy suite, using non-disposable rigid or semi-rigid instruments. Thus, it is considerably less invasive and less expensive. Today, medical thoracoscopy/pleuroscopy is increasingly used by chest physicians, mainly in patients with pleural effusion or pneumothorax including talc poudrage as best conservative pleurodesis treatment. Meanwhile, the technique is considered to be one of the main areas of interventional pneumology.
Characterisation of full-length cDNA sequences provides insights into the Eimeria tenella transcriptome
Authors: Amiruddin Nadzirah , Lee Xin-Wei , Blake Damer P , Suzuki Yutaka , Tay Yea-Ling , Lim Lik-Sin , Tomley Fiona M , Watanabe Junichi , Sugimoto Chihiro , Wan Kiew-Lian 
Published: January 2012

Abstract

Background

Eimeria tenella is an apicomplexan parasite that causes coccidiosis in the domestic fowl. Infection with this parasite is diagnosed frequently in intensively reared poultry and its control is usually accorded a high priority, especially in chickens raised for meat. Prophylactic chemotherapy has been the primary method used for the control of coccidiosis. However, drug efficacy can be compromised by drug-resistant parasites and the lack of new drugs highlights demands for alternative control strategies including vaccination. In the long term, sustainable control of coccidiosis will most likely be achieved through integrated drug and vaccination programmes. Characterisation of the E. tenella transcriptome may provide a better understanding of the biology of the parasite and aid in the development of a more effective control for coccidiosis.

Results
More than 15,000 partial sequences were generated from the 5' and 3' ends of clones randomly selected from an E. tenella second generation merozoite full-length cDNA library. Clustering of these sequences produced 1,529 unique transcripts (UTs). Based on the transcript assembly and subsequently primer walking, 433 full-length cDNA sequences were successfully generated. These sequences varied in length, ranging from 441 bp to 3,083 bp, with an average size of 1,647 bp. Simple sequence repeat (SSR) analysis identified CAG as the most abundant trinucleotide motif, while codon usage analysis revealed that the ten most infrequently used codons in E. tenella are UAU, UGU, GUA, CAU, AUA, CGA, UUA, CUA, CGU and AGU. Subsequent analysis of the E. tenella complete coding sequences identified 25 putative secretory and 60 putative surface proteins, all of which are now rational candidates for development as recombinant vaccines or drug targets in the effort to control avian coccidiosis.

Conclusions
This paper describes the generation and characterisation of full-length cDNA sequences from E. tenella second generation merozoites and provides new insights into the E. tenella transcriptome. The data generated will be useful for the development and validation of diagnostic and control strategies for coccidiosis and will be of value in annotation of the E. tenella genome sequence.