bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protein Kinase Casein Kinase 2–Mediated Upregulation of N-Cadherin Confers Anoikis Resistance on Esophageal Carcinoma Cells
Authors: Ko Hyeonseok , Kim Seongrak , Jin Cheng-Hao , Lee Eunjung , Ham Sunyoung , Yook Jong In , Kim Kunhong 
Published: July 2012

Abstract
Previously, we reported that high PKCK2 activity could protect cancer cells from death receptor–mediated apoptosis through phosphorylation of procaspase-2. Because anoikis is another form of apoptosis, we asked whether PKCK2 could similarly confer resistance to anoikis on cancer cells. Human esophageal squamous cancer cell lines with high PKCK2 activity (HCE4 and HCE7) were anoikis-resistant, whereas cell lines with low PKCK2 activity (TE2 and TE3) were anoikis-sensitive. Because the cells showed different sensitivity to anoikis, we compared the expression of cell adhesion molecules between anoikis-sensitive TE2 and anoikis-resistant HCE4 cells using cDNA microarray. We found that E-cadherin is expressed only in TE2 cells; whereas N-cadherin is expressed instead of E-cadherin in HCE4 cells. To examine whether PKCK2 activity could determine the type of cadherin expressed, we first increased intracellular PKCK2 activity in TE2 cells by overexpressing the PKCK2α catalytic subunit using lentivirus and found that high PKCK2 activity could switch cadherin expression from type E to N and confer anoikis resistance. Conversely, a decrease in PKCK2 activity in HCE4 cells by knockdown of PKCK2α catalytic subunit using shRNA induced N- to E-cadherin switching and the anoikis-resistant cells became sensitive. In addition, N-cadherin expression correlated with PKB/Akt activation and increased invasiveness. We conclude that high intracellular PKCK2 activity confers anoikis resistance on esophageal cancer cells by inducing E- to N-cadherin switching. Mol Cancer Res; 10(8); 1032–8. ©2012 AACR.
Lack of ABCG2 Shortens Latency of BRCA1-Deficient Mammary Tumors and This Is Not Affected by Genistein or Resveratrol
Authors: Zander Serge A.L. , Kersbergen Ariena , Sol Wendy , Gonggrijp Maaike , van de Wetering Koen , Jonkers Jos , Borst Piet , Rottenberg Sven 
Published: July 2012

Abstract
In addition to their role in drug resistance, the ATP-binding cassette (ABC) transporters ABCG2 and ABCB1 have been suggested to protect cells from a broad range of substances that may foster tumorigenesis. Phytoestrogens or their metabolites are substrates of these transporters and the influence of these compounds on breast cancer development is controversial. Estrogen-like properties might accelerate tumorigenesis on the one hand, whereas their proposed health-protective properties might antagonize tumorigenesis on the other. To address this issue, we used a newer generation mouse model of BRCA1-mutated breast cancer and examined tumor latency in K14cre;Brca1F/F; p53F/F, Abcb1a/b−/−;K14cre;Brca1F/F; p53F/F, or Abcg2−/−;K14cre;Brca1F/F; p53F/F animals, fed with genistein- or resveratrol-supplemented diets. Ovariectomized K14cre;Brca1F/F; p53F/F animals were included to evaluate whether any estrogen-mimicking effects can restore mammary tumor development in the absence of endogenous estrogens. Compared with the ABC transporter proficient model, ABCG2-deficient animals showed a reduced median tumor latency of 17.5 days (P &lt; 0.001), whereas no significant difference was observed for ABCB1-deficient animals. Neither genistein nor resveratrol altered this latency reduction in Abcg2−/−;K14cre;Brca1F/F; p53F/F animals. Ovariectomy resulted in nearly complete loss of mammary tumor development, which was not restored by genistein or resveratrol. Our results show that ABCG2 contributes to the protection of genetically instable epithelial cells against carcinogenesis. Diets containing high levels of genistein or resveratrol had no effect on mammary tumorigenesis, whether mice were lacking ABCG2 or not. Because genistein and resveratrol only delayed skin tumor development of ovariectomized animals, we conclude that these phytoestrogens are no effective modulators of mammary tumor development in our mouse model. Cancer Prev Res; 5(8); 1053–60. ©2012 AACR.
Association of a Genetic Risk Score With Prevalent and Incident Myocardial Infarction in Subjects Undergoing Coronary Angiography
Authors: Patel Riyaz S. , Sun Yan V. , Hartiala Jaana , Veledar Emir , Su Shaoyong , Sher Salman , Liu Ying X. , Rahman Ayaz , Patel Ronak , Rab S. Tanveer , Vaccarino Viola , Zafari A. Maziar , Samady Habib , Tang W.H. Wilson , Allayee Hooman , Hazen Stanley L. , Quyyumi Arshed A. 
Published: July 2012

Background—
Genome-wide association studies have identified multiple variants associating with coronary artery disease (CAD) and myocardial infarction (MI). Whether a combined genetic risk score (GRS) is associated with prevalent and incident MI in high-risk subjects remains to be established.

Methods and Results—

In subjects undergoing cardiac catheterization (n=2597), we identified cases with a history of MI onset at age <70 years and controls ≥70 years without prior MI and followed them for incident MI and death. Genotyping was performed for 11 established CAD/MI variants, and a GRS was calculated based on average number of risk alleles carried at each locus weighted by effect size. Replication of association findings was sought in an independent angiographic cohort (n=2702). The GRS was significantly associated with prevalent MI, occurring before age 70, compared with older controls (≥70 years of age) with no history of MI (
P
<0.001). This association was successfully replicated in a second cohort, yielding a pooled
P
value of <0.001. The GRS modestly improved the area-under–the–curve statistic in models of prevalent MI with traditional risk factors; however, the association was not statistically significant when elderly controls without MI but with s\ angiographic CAD were examined (pooled
P
=0.11). Finally, during a median 2.5-year follow-up, only a nonsignificant trend was noted between the GRS and incident events, which was also not significant in the replication cohort.

Conclusions—
A GRS of 11 CAD/MI variants is associated with prevalent MI but not near-term incident adverse events in 2 independent angiographic cohorts. These findings have implications for understanding the clinical use of genetic risk scores for secondary as opposed to primary risk prediction.
Research Radar Analyses of the Internal Boundary Layer over Cape Canaveral, Florida, during the Landfall of Hurricane Frances (2004)
Authors: Hirth Brian D. , Schroeder John L. , Weiss Christopher C. , Smith Douglas A. , Biggerstaff Michael I. 
Published: July 2012

Abstract
The structure of the coastal internal boundary layer (IBL) during a landfalling hurricane has important ramifications on operational forecasting, structural design, and poststorm damage assessment. Despite these important issues, the mean IBL structure at the coastline during landfall is poorly understood. Knowledge of the vertical kinematic structure within tropical cyclones over water has improved greatly through aircraft reconnaissance missions and the advent of GPS dropsondes and stepped frequency microwave radiometers. Unfortunately, reconnaissance and research aircraft are limited to overwater missions, resulting in a poor understanding of vertical kinematic structure near the coastal interface, where changes in IBL structure are expected due to changes in surface roughness. Composite single- and dual-Doppler radar observations collected by the Shared Mobile Atmospheric Research and Teaching Radars during the landfall of Hurricane Frances (2004) are presented. Data analyses from the Cape Canaveral, Florida, region reveal a pronounced IBL throughout the data collection period. As a result, significant variability in the analyzed wind speed and direction are found across and near the coastal interface. IBL height is found to be suppressed when compared to an accepted empirical growth model, while multiple abrupt roughness transitions associated with the Cape Canaveral region contribute to a complex mean IBL structure.
Organisational obsessive– compulsive disorder: has clinical governance become pathological?
Authors: Bender Keith 
Published: July 2012

Objective: The aim of the study was to compare the use of various monitoring tools in the public psychiatry sector to the development of obsessive–compulsive rituals in individuals. Conclusion: The step from useful data collection to meaningless and incapacitating ritual may be prevented by the use of ongoing dialogue, assumption testing, realistic appraisal of clinician responsibility and tolerance of uncertainty.
Ready to Change: a scheduled telephone counselling programme for problem gambling
Authors: Rodda Simone , Lubman Dan 
Published: July 2012

Objective: This study describes the implementation of an innovative 4–6 week cognitive behavioural therapy (CBT) programme for problem gambling, Ready to Change (RTC), delivered via telephone and workbook. Method: Participants referred into the programme during the first three years of operation had a mean age of 45 years (range 19–81 years). The majority of participants were female (56%, n=129) and had problems associated with gaming machines (81.7%, n=188). Results: Between January 2008 and December 2010, 230 people were assessed and offered the RTC programme. The main reason for referral of a person into the programme was difficulty in accessing a face-to-face agency. Conclusions: We describe the components and challenges of a 4–6 week programme for the treatment of problem gambling delivered via telephone. While distance-based treatments address concerns over access to services, further research investigating their effectiveness is required.
Suicide attempts by jumping from a height: a consultation liaison experience
Authors: Gore-Jones Victoria , O’Callaghan John 
Published: July 2012

Objective: The purpose of this research was to study the demographic and clinical characteristics of a group of patients who attempted suicide by jumping from a height and sustained injuries that required hospitalisation. Method: Participants were patients who were admitted to a large tertiary hospital in Brisbane City following a suicide attempt. Patients received treatment-as-usual and their hospital files were audited retrospectively. Results: The patient profile was of a 31-year-old single person with a diagnosis of either a psychotic illness or borderline personality disorder. Sixty percent had prior contact with a mental health service and nearly three-quarters had made a previous attempt. Eighty percent reported the attempt was impulsive and nearly three-quarters reported having suicidal intent. The majority of attempts were precipitated by interpersonal stressors. Spinal injuries were the most common result. Conclusions: Practical implications include the role of interpersonal stressors as treatment targets. The impulsive nature of the attempt also raises the issue of physical barriers to deter suicide attempts by jumping from a height.
Protein-protein binding site identification by enumerating the configurations
Authors: Guo Fei , Li Shuai Cheng , Wang Lusheng , Zhu Daming 
Published: July 2012

AbstractBackgroundThe ability to predict protein-protein binding sites has a wide range of applications, including signal transduction studies, de novo drug design, structure identification and comparison of functional sites. The interface in a complex involves two structurally matched protein subunits, and the binding sites can be predicted by identifying structural matches at protein surfaces.ResultsWe propose a method which enumerates “all” the configurations (or poses) between two proteins (3D coordinates of the two subunits in a complex) and evaluates each configuration by the interaction between its components using the Atomic Contact Energy function. The enumeration is achieved efficiently by exploring a set of rigid transformations. Our approach incorporates a surface identification technique and a method for avoiding clashes of two subunits when computing rigid transformations. When the optimal transformations according to the Atomic Contact Energy function are identified, the corresponding binding sites are given as predictions. Our results show that this approach consistently performs better than other methods in binding site identification.ConclusionsOur method achieved a success rate higher than other methods, with the prediction quality improved in terms of both accuracy and coverage. Moreover, our method is being able to predict the configurations of two binding proteins, where most of other methods predict only the binding sites. The software package is available athttp://sites.google.com/site/guofeics/dobifor non-commercial use.
Functional characterization and evolution of PTH/PTHrP receptors: insights from the chicken
Authors: Pinheiro Pedro LC , Cardoso João CR , Power Deborah M , Canário Adelino V M 
Published: July 2012

Abstract

Background
The parathyroid hormone (PTH)-family consists of a group of structurally related factors that regulate calcium and bone homeostasis and are also involved in development of organs such as the heart, mammary gland and immune system. They interact with specific members of family 2 B1 G-protein coupled receptors (GPCRs), which have been characterised in teleosts and mammals. Two PTH/PTHrP receptors, PTH1R and PTH2R exist in mammals and in teleost fish a further receptor PTH3R has also been identified. Recently in chicken, PTH-family members involved in calcium transport were characterized and specific PTHRs are suggested to exist although they have not yet been isolated or functionally characterized. The aim of this study is to further explore the evolution and function of the vertebrate PTH/PTHrP system through the isolation, phylogenetic analysis and functional characterization of the chicken receptors.

Results
Two PTHRs were isolated in chicken and sequence comparison and phylogenetic analysis indicate that the chicken receptors correspond to PTH1R and PTH3R, which emerged prior to the teleost/tetrapod divergence since they are present in cartilaginous fish. The vertebrate PTH2R receptor and its ligand TIP39 have been lost from bird genomes. Chicken PTH1R and PTH3R have a divergent and widespread tissue expression and are also evident in very early embryonic stages of development. Receptor stimulation studies using HEK293 cells stably expressing the chicken PTH1R and PTH3R and monitoring cAMP production revealed they are activated by chicken 1–34 N-terminal PTH-family peptides in a dose dependent manner. PTH-L and PTHrP were the most effective peptides in activating PTH1R (EC50 = 7.7 nM and EC50 = 22.7 nM, respectively). In contrast, PTH-L (100 nM) produced a small cAMP accumulation on activation of PTH3R but PTHrP and PTH (EC50 = 2.5 nM and EC50 = 22.1 nM, respectively) readily activated the receptor. PTHrP also stimulated intracellular Ca2+ accumulation on activation of PTH1R but not PTH3R.

Conclusion
Two PTHR homologues of the vertebrate PTH1R and PTH3R were isolated and functionally characterized in chicken. Their distinct pattern of expression during embryo development and in adult tissues, together with their ligand preference, suggests that they have acquired specific functions, which have contributed to their maintenance in the genome. PTH2R and its activating ligand, TIP39, are absent from bird genomes. Nonetheless identification of putative PTH2R and TIP39 in the genome of an ancient agnathan, lamprey, suggests the PTH/PTHrP ligand and receptor family was already present in an early basal paraphyletic group of vertebrates and during the vertebrate radiation diverged via gene/genome duplication and deletion events. Knowledge of the role PTH/PTHrP system in early vertebrates will help to establish evolution of function.
Duplicate gene evolution, homoeologous recombination, and transcriptome characterization in allopolyploid cotton
Authors: Flagel Lex E , Wendel Jonathan F , Udall Joshua A 
Published: July 2012

Abstract

Background
Modern allotetraploid cotton contains an “A” and “D” genome from an ancestral polyploidy event that occurred approximately 1–2 million years ago. Diploid A- and D-genome species can be compared to the A- and D-genomes found within these allotetraploids to make evolutionary inferences about polyploidy. In this paper we present a comprehensive EST assembly derived from diploid and model allotetraploid cottons and demonstrate several evolutionary inferences regarding genic evolution that can be drawn from these data.

Results
We generated a set of cotton expressed sequence tags (ESTs), comprising approximately 4.4 million Sanger and next-generation (454) transcripts supplemented by approximately 152 million Illumina reads from diploid and allotetraploid cottons. From the EST alignments we inferred 259,192 genome-specific single nucleotide polymorphisms (SNPs). Molecular evolutionary analyses of protein-coding regions demonstrate that the rate of nucleotide substitution has increased among both allotetraploid genomes relative to the diploids, and that the ratio of nonsynonymous to synonymous substitutions has increased in one of the two polyploid lineages we sampled. We also use these SNPs to show that a surprisingly high percentage of duplicate genes (~7 %) show a signature of non-independent evolution in the allotetraploid nucleus, having experienced one or more episodes of nonreciprocal homoeologous recombination (NRHR).

Conclusions
In this study we characterize the functional and mutational properties of the cotton transcriptome, produce a large genome-specific SNP database, and detect illegitimate genetic exchanges between duplicate genomes sharing a common allotetraploid nucleus. Our findings have important implications for our understanding of the consequences of polyploidy and duplicate gene evolution. We demonstrate that cotton genes have experienced an increased rate of molecular evolution following duplication by polyploidy, and that polyploidy has enabled considerable levels of nonreciprocal exchange between homoeologous genes.
hTERT, MYC and TP53 deregulation in gastric preneoplastic lesions
Authors: Silva Tanielly Cristina Raiol , Leal Mariana Ferreira , Calcagno Danielle Queiroz , de Souza Carolina Rosal Teixeira , Khayat André Salim , dos Santos Ney Pereira Carneiro , Montenegro Raquel Carvalho , Rabenhorst Silvia Helena Barem , Nascimento Mayara Quaresma , Assumpção Paulo Pimentel , de Arruda Cardoso Smith Marília , Burbano Rommel Rodríguez 
Published: July 2012

Abstract

Background
Gastric cancer is a serious public health problem in Northern Brazil and in the world due to its high incidence and mortality. Despite the severity of the disease, more research is needed to better understand the molecular events involved in this intestinal-type gastric carcinogenesis process. Since precancerous lesions precede intestinal-type gastric cancer, here, we evaluated the hTERT, MYC, and TP53 mRNA and protein expression, as well as TP33 copy number, in gastric preneoplastic lesions.

Methods
We evaluated 19 superficial gastritis, 18 atrophic gastritis, and 18 intestinal metaplasia from cancer-free individuals of Northern Brazil. Quantitative reverse transcription PCR was used to analyze the mRNA expression and immunohistochemical methods were used to assess protein immunoreactivity in tissue samples. The number of TP53 gene copies was investigated in gastric diseases by quantitative PCR.

Results
We observed hTERT, MYC, and p53 immunoreactivity only in intestinal metaplasia samples. The immunoreactivity of these proteins was strongly associated with each other. A significantly higher MYC mRNA expression was observed in intestinal metaplasia compared to gastritis samples. Loss of TP53 was also only detected in intestinal metaplasia specimens.

Conclusions
We demonstrated that hTERT, MYC, and TP53 are deregulated in intestinal metaplasia of individuals from Northern Brazil and these alterations may facilitate tumor initiation.
Different fatty acid metabolism effects of (−)-Epigallocatechin-3-Gallate and C75 in Adenocarcinoma lung cancer
Authors: Relat Joana , Blancafort Adriana , Oliveras Glòria , Cufí Sílvia , Haro Diego , Marrero Pedro F , Puig Teresa 
Published: July 2012

Abstract

Background
Fatty acid synthase (FASN) is overexpressed and hyperactivated in several human carcinomas, including lung cancer. We characterize and compare the anti-cancer effects of the FASN inhibitors C75 and (−)-epigallocatechin-3-gallate (EGCG) in a lung cancer model.

Methods
We evaluated in vitro the effects of C75 and EGCG on fatty acid metabolism (FASN and CPT enzymes), cellular proliferation, apoptosis and cell signaling (EGFR, ERK1/2, AKT and mTOR) in human A549 lung carcinoma cells. In vivo, we evaluated their anti-tumour activity and their effect on body weight in a mice model of human adenocarcinoma xenograft.

Results
C75 and EGCG had comparable effects in blocking FASN activity (96,9% and 89,3% of inhibition, respectively). In contrast, EGCG had either no significant effect in CPT activity, the rate-limiting enzyme of fatty acid β-oxidation, while C75 stimulated CPT up to 130%. Treating lung cancer cells with EGCG or C75 induced apoptosis and affected EGFR-signaling. While EGCG abolished p-EGFR, p-AKT, p-ERK1/2 and p-mTOR, C75 was less active in decreasing the levels of EGFR and p-AKT. In vivo, EGCG and C75 blocked the growth of lung cancer xenografts but C75 treatment, not EGCG, caused a marked animal weight loss.

Conclusions
In lung cancer, inhibition of FASN using EGCG can be achieved without parallel stimulation of fatty acid oxidation and this effect is related mainly to EGFR signaling pathway. EGCG reduce the growth of adenocarcinoma human lung cancer xenografts without inducing body weight loss. Taken together, EGCG may be a candidate for future pre-clinical development.
Effects of particulate matter on inflammatory markers in the general adult population
Authors: Tsai Dai-Hua , Amyai Nadia , Marques-Vidal Pedro , Wang Jia-Lin , Riediker Michael , Mooser Vincent , Paccaud Fred , Waeber Gerard , Vollenweider Peter , Bochud Murielle 
Published: July 2012

Abstract

Background
Particulate air pollution is associated with increased risk of cardiovascular disease and stroke. Although the precise mechanisms underlying this association are still unclear, the induction of systemic inflammation following particle inhalation represents a plausible mechanistic pathway.

Methods
We used baseline data from the CoLaus Study including 6183 adult participants residing in Lausanne, Switzerland. We analyzed the association of short-term exposure to PM10 (on the day of examination visit) with continuous circulating serum levels of high-sensitive C-reactive protein (hs-CRP), interleukin 1-beta (IL-1β), interleukin 6 (IL-6), and tumor-necrosis-factor alpha (TNF-α) by robust linear regressions, controlling for potential confounding factors and assessing effect modification.

Results
In adjusted analyses, for every 10 μg/m3 elevation in PM10, IL-1ß increased by 0.034 (95 % confidence interval, 0.007-0.060) pg/mL, IL-6 by 0.036 (0.015-0.057) pg/mL, and TNF-α by 0.024 (0.013-0.035) pg/mL, whereas no significant association was found with hs-CRP levels.

Conclusions
Short-term exposure to PM10 was positively associated with higher levels of circulating IL-1ß, IL-6 and TNF-α in the adult general population. This positive association suggests a link between air pollution and cardiovascular risk, although further studies are needed to clarify the mechanistic pathway linking PM10 to cardiovascular risk.