bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synergistic Activation of the Inhibin α-Promoter by Steroidogenic Factor-1 and Cyclic Adenosine 3′,5′-Monophosphate
Authors: Ito Masafumi , Park Youngkyu , Weck Jennifer , Mayo Kelly E. , Jameson J. Larry 
Published: January 2014

AbstractThe inhibin α-subunit gene is expressed in the ovary, testis, adrenal, and pituitary. Because this pattern of expression corresponds to that of the orphan nuclear receptor, steroidogenic factor-1 (SF-1), we hypothesized that the inhibin α promoter might be regulated by SF-1. Expression of exogenous SF-1, in an SF-1 deficient cell line, caused modest stimulation of the inhibinα promoter. However, activation of the cAMP pathway, which is known to regulate inhibin α expression, greatly enhanced the actions of SF-1. Coexpression of SF-1 with the catalytic subunit of cAMP-dependent protein kinase A caused greater than 250-fold stimulation, whereas only 4- or 7-fold stimulation was seen by the SF-1 or protein kinase A pathway alone. Synergistic stimulation by SF-1 and the cAMP pathway was also seen in GRMO2 granulosa cells, which express endogenous SF-1. Deletion and site-directed mutagenesis localized a novel SF-1 regulatory element (TCA GGGCCA; −137 to −129) adjacent to a variant cAMP-response element (CRE; −120 to −114). The synergistic property of SF-1 and cAMP stimulation was inherent within this composite inhibin α fragment (−146 and −112), as it was transferable to heterologous promoters. Mutations in either the CRE or the SF-1 regulatory element completely eliminated synergistic activation by these pathways. The binding of SF-1 and CRE binding protein (CREB) to the inhibin α regulatory elements was relatively weak in gel mobility shift assays, consistent with their deviation from consensus binding sites. However, SF-1 was found to interact with CREB using an assay in which epitope-tagged SF-1 was expressed in cells and used to pull down in vitro translated CREB. Expression of CREB binding protein (CBP), a coactivator that interacts with SF-1 and CREB, further enhanced transcription by these pathways. Stimulation by the SF-1 and cAMP pathways was associated with increased histone H4 acetylation, suggesting that chromatin remodeling accompanies their actions. We propose a model in which direct interactions of SF-1, CREB, and associated coactivators like CBP induce strongly cooperative transactivation by pathways that individually have relatively weak effects on transcription.
Chronic Elevation of Calmodulin in the Ventricles of Transgenic Mice Increases the Autonomous Activity of Calmodulin-Dependent Protein Kinase II, Which Regulates Atrial Natriuretic Factor Gene Expression
Authors: Colomer Josep M. , Means Anthony R. 
Published: January 2014

AbstractAlthough isoforms of Ca2+/calmodulin-dependent protein kinase II (CaMKII) have been implicated in the regulation of gene expression in cultured cells, this issue has yet to be addressed in vivo. We report that the overexpression of calmodulin in ventricular myocytes of transgenic mice results in an increase in the Ca2+/calmodulin-independent activity of endogenous CaMKII. The calmodulin transgene is regulated by a 500-bp fragment of the atrial natriuretic factor (ANF) gene promoter which, based on cell transfection studies, is itself known to be regulated by CaMKII. The increased autonomous activity of CaMKII maintains the activity of the transgene and establishes a positive feedforward loop, which also extends the temporal expression of the endogenous ANF promoter in ventricular myocytes. Both the increased activity of CaMKII and transcriptional activation of ANF are highly selective responses to the chronic overexpression of calmodulin. These results indicate that CaMKII can regulate gene expression in vivo and suggest that this enzyme may represent the Ca2+-dependent target responsible for reactivation of the ANF gene during ventricular hypertrophy.
Hepatic Nuclear Factor-3 (HNF-3 or Foxa2) Regulates Glucagon Gene Transcription by Binding to the G1 and G2 Promoter Elements
Authors: Gauthier Benoit R. , Schwitzgebel Valerie M. , Zaiko Maia , Mamin Aline , Ritz-Laser Beate , Philippe Jacques 
Published: January 2014

AbstractGlucagon gene expression in the endocrine pancreas is controlled by three islet-specific elements (G3, G2, and G4) and theα -cell-specific element G1. Two proteins interacting with G1 have previously been identified as Pax6 and Cdx2/3. We identify here the third yet uncharacterized complex on G1 as hepatocyte nuclear factor 3 (HNF-3)β, a member of the HNF-3/forkhead transcription family, which plays an important role in the development of endoderm-related organs. HNF-3 has been previously demonstrated to interact with the G2 element and to be crucial for glucagon gene expression; we thus define a second binding site for this transcription on the glucagon gene promoter. We demonstrate that both HNF-3α and -β produced in heterologous cells can interact with similar affinities to either the G1 or G2 element. Pax6, which binds to an overlapping site on G1, exhibited a greater affinity as compared with HNF-3α or -β. We show that both HNF-3β and -α can transactivate glucagon gene transcription through the G2 and G1 elements. However, HNF-3 via its transactivating domains specifically impaired Pax6-mediated transactivation of the glucagon promoter but had no effect on transactivation by Cdx2/3. We suggest that HNF-3 may play a dual role on glucagon gene transcription by 1) inhibiting the transactivation potential of Pax6 on the G1 and G3 elements and 2) direct activation through G1 and G2.
Estrogen Action Via the G Protein-Coupled Receptor, GPR30: Stimulation of Adenylyl Cyclase and cAMP-Mediated Attenuation of the Epidermal Growth Factor Receptor-to-MAPK Signaling Axis
Authors: Filardo Edward J. , Quinn Jeffrey A. , Frackelton A. Raymond , Bland Kirby I. 
Published: January 2014

AbstractEstrogen triggers rapid yet transient activation of the MAPKs, extracellular signal-regulated kinase (Erk)-1 and Erk-2. We have reported that this estrogen action requires the G protein-coupled receptor, GPR30, and occurs via Gβγ-subunit protein-dependent transactivation of the epidermal growth factor (EGF) receptor through the release of pro-heparan-bound EGF from the cell surface. Here we investigate the mechanism by which Erk-1/-2 activity is rapidly restored to basal levels after estrogen stimulation. Evidence is provided that attenuation of Erk-1/-2 activity by estrogen occurs via GPR30-dependent stimulation of adenylyl cyclase and cAMP-dependent signaling that results in Raf-1 inactivation. We show that 17β-E2 represses EGF-induced activation of the Raf-to-Erk pathway in human breast carcinoma cells that express GPR30, including MCF-7 and SKBR3 cells which express both or neither, ER, respectively. MDA-MB-231 cells, which express ERβ, but not ERα, and low levels of GPR30 protein, are unable to stimulate adenylyl cyclase or promote estrogen-mediated blockade of EGF-induced activation of Erk-1/-2. Pretreatment of MDA-MB-231 cells with cholera toxin, which ADP-ribosylates and activates Gαs subunit proteins, results in G protein-coupled receptor (GPCR)-independent adenylyl cyclase activity and suppression of EGF-induced Erk-1/-2 activity. Transfection of GPR30 into MDA-MB-231 cells restores their ability to stimulate adenylyl cyclase and attenuate EGF-induced activation of Erk-1/-2 by estrogen. Moreover, GPR30-dependent, cAMP-mediated attenuation of EGF-induced Erk-1/-2 activity was achieved by ER antagonists such as tamoxifen or ICI 182, 780; yet not by 17α-E2 or progesterone. Thus, our data delineate a novel mechanism, requiring GPR30 and estrogen, that acts to regulate Erk-1/-2 activity via an inhibitory signal mediated by cAMP. Coupled with our prior findings, these current data imply that estrogen balances Erk-1/-2 activity through a single GPCR via two distinct G protein-dependent signaling pathways that have opposing effects on the EGF receptor-to-MAPK pathway.
PRL Modulates Cell Cycle Regulators in Mammary Tumor Epithelial Cells
Authors: Schroeder Matthew D. , Symowicz Jaime , Schuler Linda A. 
Published: January 2014

Abstract
PRL is essential for normal lobulo-alveolar growth of the mammary gland and may contribute to mammary cancer development or progression. However, analysis of the mechanism of action of PRL in these processes is complicated by the production of PRL within mammary epithelia. To examine PRL actions in a mammary cell-specific context, we selected MCF-7 cells that lacked endogenous PRL synthesis, using PRL stimulation of interferon-γ-activated sequence-related PRL response elements. Derived clones exhibited a greater proliferative response to PRL than control cells. To understand the mechanism, we examined, by Western analysis, levels of proteins essential for cell cycle progression as well as phosphorylation of retinoblastoma protein. The expression of cyclin D1, a critical regulator of the G1/S transition, was significantly increased by PRL and was associated with hyperphosphorylation of retinoblastoma protein at Ser780. Cyclin B1 was also increased by PRL. In contrast, PRL decreased the Cip/Kip family inhibitor, p21, but not p16 or p27. These studies demonstrate that PRL can stimulate the cell cycle in mammary epithelia and identify specific targets in this process. This model system will enable further molecular dissection of the pathways involved in PRL-induced proliferation, increasing our understanding of this hormone and its interactions with other factors in normal and pathogenic processes.
14-3-3 Facilitates Insulin-Stimulated Intracellular Trafficking of Insulin Receptor Substrate 1
Authors: Xiang Xiaoqin , Yuan Mingsheng , Song Ying , Ruderman Neil , Wen Rong , Luo Zhijun 
Published: January 2014

AbstractThe appearance of a complex between tyrosine-phosphorylated insulin receptor substrate 1 (IRS-1) and PI3K in a high-speed pellet fraction (HSP) is thought to be a key event in insulin action. Conversely, the disappearance of the IRS-1/PI3K complex from this fraction has been linked to insulin desensitization. The present study examines the role of 14-3-3, a specific phospho-serine binding protein, in mediating the disappearance of IRS-1 from the HSP after insulin treatment. An in vitro pull-down assay using recombinant 14-3-3 revealed that insulin enhances the association of 14-3-3 with IRS-1 in cultured adipocytes and that this is completely inhibited by wortmannin. An association of IRS-1 and 14-3-3 was also observed and was maximal after stimulation by insulin, when endogenous proteins were immunoprecipitated. Epidermal growth factor (EGF), 12-O-tetradecanoylphorbol-13-acetate, and okadaic acid, other agents that cause serine/threonine phosphorylation of IRS-1, also stimulated IRS binding to 14-3-3. The enhancement of IRS-1 binding to 14-3-3 by insulin was accompanied by movement of IRS-1 and the p85 subunit of PI3K from the HSP to the cytosol. In keeping with a key role of 14-3-3 in mediating this redistribution of IRS-1, the complexes of IRS-1 and 14-3-3 were found in the cytosol but not in the HSP of insulin-treated cells. In addition, colocalization of IRS-1 and 14-3-3 was observed in the cytoplasm after insulin treatment by confocal microscopy. Finally, the addition of a phosphorylated 14-3-3 binding peptide to an adipocyte homogenate (to remove 14-3-3 from IRS-1) increased the abundance of IRS-1/PI3K complexes in the HSP and decreased their abundance in the cytosol. These findings strongly suggest that 14-3-3 participates in the intracellular trafficking of IRS-1 by promoting the displacement of serine-phosphorylated IRS-1 from particular structures. They also suggest that 14-3-3 proteins could play an integral role in the process of insulin desensitization.
Ovulatory Surges of Human CG Prevent Hormone-Induced Granulosa Cell Tumor Formation Leading to the Identification of Tumor-Associated Changes in the Transcriptome
Authors: Owens Gabe E. , Keri Ruth A. , Nilson John H. 
Published: January 2014

AbstractGranulosa cell tumors comprise approximately 10% of ovarian tumors and, although rare, are clinically important due to their potential for malignancy and recurrence. Although their morphological features have been carefully described, the global changes in gene expression associated with their formation remain undetermined. To initiate this characterization, we used a transgenic mouse model in which granulosa cell tumors occur with 100% penetrance in CF-1 mice that harbor a novel transgene encoding a chimeric LHβ subunit. When this transgene is expressed in other strains of mice, including (C57BL/6♀ × CF-1♂,Tg) F1 hybrids, luteomas develop even though levels of LH remain high. This dichotomous response permits a longitudinal comparison of global changes in transcriptomes uniquely associated with either granulosa cell tumors or luteomas. Herein we report numerous changes in the transcriptome, including a decrease in LH receptor mRNA and increases in several mRNAs that encode secreted proteins previously associated with granulosa cell tumors. Furthermore, we identified a constellation of mRNAs that encode proteins that may serve as new markers for this tumor phenotype. Additional experiments indicated that periodic treatment with human CG prevented formation of granulosa cell tumors in mice genetically predisposed to tumor development and, instead, led to the appearance of luteomas. More importantly, ovarian transcriptomes from the luteomas induced by ovulatory doses of human CG permitted refined confirmation of gene expression changes that were uniquely associated with either granulosa cell tumors in the permissive CF-1 genetic background or in luteomas in the F1 hybrids. Together, these dynamic changes in the ovarian transcriptome indict various signaling pathways potentially involved in mediating the actions of LH over time and, depending on genetic background, the formation of either a luteoma or a granulosa cell tumor.
Functional Microarray Analysis of Mammary Organogenesis Reveals a Developmental Role in Adaptive Thermogenesis
Authors: Master Stephen R. , Hartman Jennifer L. , D’Cruz Celina M. , Moody Susan E. , Keiper Elizabeth A. , Ha Seung I. , Cox James D. , Belka George K. , Chodosh Lewis A. 
Published: January 2014

AbstractThe use of DNA microarrays to study vertebrate organogenesis presents unique analytical challenges compared with expression profiling of homogeneous cell populations. We have used a general approach that permits the automated, unbiased identification of biologically relevant patterns of gene expression to study murine mammary gland development. Our studies confirm the utility of this approach by demonstrating the ready identification of cellular processes and pathways of known functional importance in mammary development. Additionally, this approach permitted the identification of genetic pathways with unpredicted patterns of developmental regulation, including those involved in angiogenesis, extracellular matrix synthesis, and the β-oxidation of fatty acids. Surprisingly, our findings demonstrate that the coordinate regulation of genes involved in the β-oxidation of fatty acids reflects the presence of an abundant, yet previously unrecognized stromal compartment within the mammary gland that is composed of brown adipose tissue. Our data demonstrate that the amount of brown adipose tissue present in the mammary gland is developmentally regulated; that PPARα, Ucp1, and genes involved in fatty acid oxidation are spatially and temporally coregulated during development; that the mammary gland plays a functional role in adaptive thermogenesis; and that the transcriptional control of this adaptive response to cold is itself developmentally regulated.
Synergistic Action of Prolactin (PRL) and Androgen on PRL-Inducible Protein Gene Expression in Human Breast Cancer Cells: A Unique Model for Functional Cooperation between Signal Transducer and Activator of Transcription-5 and Androgen Receptor
Authors: Carsol Jean-Louis , Gingras Sébastien , Simard Jacques 
Published: January 2014

AbstractThe signal transducer and activator of transcription 5 (Stat5) has been shown to cooperate with some nuclear receptors. However, an interaction has never been demonstrated with the androgen receptor (AR). Given that the PRL-inducible protein/gross cystic disease fluid-15 (PIP/GCDFP-15) is both a PRL-controlled and an androgen-controlled protein, we used its promoter region to investigate the potential interaction between Stat5 and androgen receptor. Dihydrotestosterone or PRL alone slightly modulated or did not modulate the luciferase activity of all reporter gene constructs. In contrast, a maximal increase was observed using the −1477+42 reporter gene construct after exposure to both dihydrotestosterone and PRL. The requirement of half-site androgen-responsive elements and two consensus Stat5-binding elements, Stat5#1 and Stat5#2, was determined by site-directed mutagenesis. Activated Stat5B binds with a higher affinity to Stat5#2 than to Stat5#1. Stat5AΔ749 and Stat5BΔ754 mutants demonstrated that the Stat5 trans-activation domain is involved in the hormonal cooperation. The cooperation depends on the PRL-induced phosphorylation on Tyr694 in Stat5A and Tyr699 in Stat5B, as demonstrated using the Stat5AY694F and Stat5BY699F proteins. The use of AR Q798E, C619Y, and C784Y mutants showed that trans-activation, DNA-binding, and ligand-binding domains of AR are essential. Our study thus suggests a functional cooperation between AR and Stat5.
Estrogen Receptor α and Aromatase Polymorphisms Affect Risk, Prognosis, and Therapeutic Outcome in Men with Castration-Resistant Prostate Cancer Treated with Docetaxel-Based Therapy
Authors: Sissung Tristan M. , Danesi Romano , Kirkland C. Tyler , Baum Caitlin E. , Ockers Sandra B. , Stein Erica V. , Venzon David , Price Douglas K. , Figg William D. 
Published: January 2014

Abstract

Context
Reactive estrogen species cause genotoxicity and interfere with docetaxel-mediated tubulin polymerization resulting in shortened survival in men with castrate-resistant prostate cancer (CRPC).

Objective
We hypothesized that polymorphisms in estrogen synthesis and estrogen targets (i.e., CYP19 and ERα) would be linked to interindividual variation in CRPC risk, docetaxel response, and overall survival (OS) in men with CRPC.

Materials and Methods
Patients with CRPC (n = 115) treated with docetaxel, single-agent thalidomide (n = 42), or healthy controls (n = 289) were genotyped for the CYP19 R264C (rs700519) and the ERα PvuII T&gt; C (rs2234693) and XbaI A&gt; G (rs9340799) polymorphisms.

Results
Patients carrying two copies of ERα polymorphisms had shorter progression-free survival on docetaxel than other patients (median survival difference ≥3.1 months; P ≤ 0.036). When the analysis was limited to nonobese patients, the relationship between the ERα XbaI A&gt; G polymorphism and PFS improved (median survival difference = 3.5 months; P = 0.0078). The CYP19 R264C variant was related to the duration of survival after docetaxel in patients who were &gt; 70 years old (median survival difference = 10.6 months; P = 0.041). Both ERα polymorphisms were also associated with increases in CRPC risk [P ≤ 0.032; double variants vs. wild-type odds ratio (OR) ≥ 2.6], and the association with the ERα PvuII T&gt; C also improved in those men who were &lt; 70 years old (P = 0.0073; OR = 3.0).

Conclusions
This study demonstrates that estrogen-related genetic variation affects docetaxel clinical response and that this relationship is dependent on age and body-type in men with CRPC. Moreover, this study suggests ERα polymorphisms confer risk of developing prostate cancer, especially in men under 70 years of age.
Photocatalytic Activity of Rutile Titania for Hydrogen Evolution
Authors: Amano Fumiaki , Nakata Masashi , Ishinaga Eri 
Published: January 2014

Abstract
Herein, we demonstrate the high photocatalytic activity of rutile particles for H2 evolution from aqueous ethanol solution. The rutile particles were prepared by successive calcination at 900 °C and H2 reduction treatment at 700 °C of commercial anatase-rich TiO2 powder, Evonik/Degussa P25.
Silica-supported Tripod Triarylphosphines: Application to Palladium-catalyzed Borylation of Chloroarenes
Authors: Iwai Tomohiro , Harada Tomoya , Tanaka Ryotaro , Sawamura Masaya 
Published: January 2014

Abstract
Silica-supported tripod triarylphosphines that have a Ph3P-type core tripodally immobilized on a silica surface enabled the Pd-catalyzed borylation of chloroarenes with bis(pinacolato)diboron under mild conditions. The immobilization in tripod was crucial for the excellent performance of the Ph3P-based ligands.
Aggression and self-aggression syndrome in females suffering from bulimia nervosa
Authors: Izydorczyk Bernadetta 
Published: January 2014

Abstract
The current study is aimed at creating a psychological profile of characteristics of aggressive and self-aggressive behaviour exhibited by females with bulimia, as well as conducting a comparative analysis of the differences between bulimic females and individuals displaying no mental disorders in terms of the major characteristics of aggressive and selfaggressive behaviour. The methods: the Buss-Durkee Hostility-Guilt Inventory, the Psychological Inventory of Aggression Syndrome by Zbigniew. B. Gaś. The data analysis revealed significant differences between the females suffering from bulimia and the subjects displaying no mental disorders in terms of the level of aggressive and self-aggressive tendencies. It was discovered that the control participants exhibited an appropriate level of aggressive behaviour as opposed to the subjects with bulimia.
Association between social support and temperament and the intensity of PTSD symptoms in a sample of HIV positives
Authors: Rzeszutek Marcin , Oniszczenko Włodzimierz 
Published: January 2014

Abstract
The aim of this study was to investigate the association between temperament and social support and the level of quantitatively rated PTSD symptoms in a sample of HIV+ and HIV/AIDS men and women. A total of 310 men and women, including 182 HIV+ and 128 HIV/AIDS, were studied. Social support was assessed with the Berlin Social Support Scales (BSSS). Temperament was assessed with the Formal Characteristics of Behaviour - Temperament Inventory (FCBTI). Intensity of PTSD symptoms was assessed with the PTSDF (PTSD Factorial Version inventory). The best predictors of intensity of PTSD symptoms in HIV+ participants were support seeking and sensory sensitivity. Support seeking was positively associated, and sensory sensitivity was negatively associated with intensity of PTSD symptoms.
Male homophobia, touch, and compliance: A matter of the touched, not the toucher
Authors: Dolinski Dariusz 
Published: January 2014

Abstract
Numerous studies have shown that people are more likely to fulfill requests made by a stranger when he or she touches their arm or forearm slightly while asking. In Poland, however, where male homophobia is widespread, interpersonal touch decreases compliance when man touches another man. It has also been demonstrated in previous studies that highly homophobic male participants are especially unwilling to fulfill requests while touched. In this paper the hypothesis that also confederates’ homophobia create an additional factor inhibiting compliance with request formulated by men touching other men was tested in two experiments. No relations, however, was found between confederates’ level of homophobia and participants’ reaction.