bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptional Regulation of Vascular Endothelial Growth Factor Expression in Epithelial and Stromal Cells during Mouse Mammary Gland Development
Authors: Hovey Russell C. , Goldhar Anita S. , Baffi Judit , Vonderhaar Barbara K. 
Published: January 2014

AbstractAccompanying changes in the development and function of the mammary gland is the establishment of a vascular network of critical importance for lactogenesis and tumorigenesis. A potent angiogenic and permeability factor that regulates vascular development in association with epithelial-stromal interactions is vascular endothelial growth factor (VEGF). Analysis of VEGF transcription by RT-PCR revealed mRNA for all three VEGF isoforms (VEGF120, 164, 188) within the mammary gland of nulliparous females. During pregnancy the level of VEGF188 declined and became undetectable during lactation in association with the increased abundance of VEGF120 and VEGF164 mRNAs. All three isoforms were expressed at consistent levels within the cleared mammary fat pad throughout development. Furthermore, the presence of VEGF188 mRNA in omental adipose tissue at various stages established that VEGF188 is expressed specifically in adipose tissue within the mammary gland. Using 3T3-L1 preadipocytes it was demonstrated that VEGF188 mRNA transcription occurs as a late event during lipogenesis distinct from earlier induction of VEGF120 and VEGF164 mRNA during differentiation. In contrast, HC11 mammary epithelial cells only expressed mRNA for VEGF120 and VEGF164. Localization of VEGF mRNA and protein revealed that VEGF is expressed in stromal cells of the mammary gland in nulliparous females and then undergoes a transition to epithelial expression during lactation. By contrast, mRNA for the VEGF receptors, Flk-1 and Flt-1, localized to stromal cells within the mammary fat pad during virgin and gestational development and was expressed in the interstitial tissue basal to epithelial cells during lactation. Taken together, these results support the conclusion that VEGF is differentially transcribed by specific cell types within the mammary gland, and that under hormonal regulation it functions in an autocrine/paracrine manner.
Transcriptional Regulation of the Human PRL-Releasing Peptide (PrRP) Receptor Gene by a Dopamine 2 Receptor Agonist: Cloning and Characterization of the Human PrRP Receptor Gene and Its Promoter Region
Authors: Ozawa Atsushi , Yamada Masanobu , Satoh Teturou , Monden Tsuyoshi , Hashimoto Koshi , Kohga Hideaki , Hashiba Yasuhiro , Sasaki Tomio , Mori Masatomo 
Published: January 2014

AbstractPRL-releasing peptide receptor (PrRPR) mRNA was expressed in pituitary adenomas but was not detected in patients treated with bromocriptine, a specific agonist of dopamine 2 (D2) receptor. Although medical treatment with bromocriptine is effective for patients with pituitary adenomas, little is known about the molecular mechanisms of gene regulation mediated by D2 receptors. The cloned human PrRPR gene spanned approximately 2.0 kb and contained two exons and one intron. Two functional polyadenylation signals located at 510 and 714 bp downstream from the stop codon. A primer extension analysis demonstrated two major transcriptional start sites at 139 and 140 bp upstream from the translational start site and an additional minor site at −161. The promoter region contained several putative binding sites for transcriptional factors including pituitary-specific transcription factor (Pit 1), activator protein 1 (AP-1), and specificity protein (Sp1), but no typical TATA or CAAT box. This promoter showed the strong activity in the pituitary-derived GH4C1 cells, and the region between −697 and −596 bp was responsible for the stimulation both by forskolin and overexpression of cAMP response element binding protein (CREB). These stimulations were significantly suppressed by incubation with bromocriptine in a dose- and time-dependent manner, and the mutant CREB (S133A) completely abolished the inhibitory events of bromocriptine. However, EMSA studies demonstrated that CREB did not bind to this region, to which an approximately 60-kDa protein was strongly bound, and that antibodies against CREB, c-Fos, and Sp1 did not supershift this complex. Furthermore, the amount of this unknown protein was apparently reduced by treatment with bromocriptine. A series of mutation analyses demonstrated that the specific sequence, 5′-cccacatcat-3′, was required for both the binding to the 60-kDa protein and the repression by bromocriptine. Therefore, the transcriptional repression of the PrRPR gene by bromocriptine required CREB but was independent of direct binding of CREB to the gene and that the sequence −663∼−672, 5′-cccacatcat-3′, bound to the 60-kDa protein appeared to be critical for this event.
Multiprotein Bridging Factor-1 (MBF-1) Is a Cofactor for Nuclear Receptors that Regulate Lipid Metabolism
Authors: Brendel Carole , Gelman Laurent , Auwerx Johan 
Published: January 2014

AbstractMultiprotein bridging factor (MBF-1) is a cofactor that was first described for its capacity to modulate the activity of fushi tarazu factor 1, a nuclear receptor originally implicated in Drosophila development. Recently, it has been shown that human MBF-1 stimulates the transcriptional activity of steroidogenic factor 1, a human homolog of fushi tarazu factor 1, which is implicated in steroidogenesis. Here we show that this cofactor enhances the transcriptional activity of several nonsteroid nuclear receptors that are implicated in lipid metabolism, i.e. the liver receptor homolog 1, the liver X receptor α, and PPARγ. MBF-1 interacts with distinct domains in these receptors, depending on whether the receptor binds DNA as a monomer or as a heterodimer with RXR. MBF-1 does not possess any of the classical histone modifying activities such as histone acetyl- or methyl transferase activities, linked to chromatin remodeling, but interacts in vitro with the transcription factor IID complex. MBF-1 seems therefore to act as a bridging factor enabling interactions of nuclear receptors with the transcription machinery.
Potential Role of Nuclear Factor κB and Reactive Oxygen Species in cAMP and Cytokine Regulation of Surfactant Protein-A Gene Expression in Lung Type II Cells
Authors: Islam Kazi Nazrul , Mendelson Carole R. 
Published: January 2014

AbstractThe human surfactant protein-A2 (hSP-A2) gene is developmentally regulated, expressed in type II pneumonocytes, and induced by cAMP. cAMP induction of hSP-A2 expression is O2 dependent and mediated by increased phosphorylation, DNA binding, and transcriptional activation of thyroid transcription factor-1 (TTF-1). The TTF-1-binding element (TBE) at −175 bp contains a reverse-oriented nuclear factor-κB (NF-κB) binding site. IL-1 increased SP-A expression in lung type II cells and had additive stimulatory effects with cAMP. Nuclear extracts from cAMP- or IL-1-treated type II cells manifested increased binding to NF-κB consensus and TBE probes; cAMP and IL-1 had additive effects. Competitive and antibody supershift EMSA revealed that NF-κB and TTF-1 interact with TBE. IL-1 treatment of type II cells caused rapid (1 h) increases in nuclear levels of NF-κB (p50 and p65) and in binding to NF-κB and TBE probes; nuclear levels of TTF-1 were unaffected. Bt2cAMP increased binding to NF-κB and TBE probes more slowly; no changes in nuclear levels of p50, p65, or TTF-1 were evident, suggesting that IL-1 and cAMP act by different mechanisms. A role for endogenous NF-κB in cAMP and IL-1 regulation of SP-A was suggested by findings that dominant-negative forms of inhibitor of κB reduced binding of type II cell nuclear proteins to TBE and inhibited SP-A expression. In cotransfection assays, NF-κB and TTF-1 cooperatively interacted at TBE to stimulate SP-A promoter activity; this was further enhanced by IL-1. In coimmunoprecipitation assays using type II cell nuclear extracts, TTF-1 was found to interact with p65 in vivo. Finally, antioxidant inhibitors of NF-κB reduced type II cell nuclear protein binding to TBE and blocked stimulatory effects of cAMP on SP-A expression. This provides intriguing evidence that permissive effects of O2/reactive oxygen species on cAMP regulation of SP-A expression may be mediated by cooperative interactions of TTF-1 and NF-κB at the TBE.
Peptide YY (PYY) Gene Polymorphisms in the 3′-Untranslated Region and Proximal Promoter Regions Regulate Cellular Gene Expression and PYY Secretion and Metabolic Syndrome Traits in Vivo
Authors: Shih Pei-an Betty , Wang Lei , Chiron Stephane , Wen Gen , Nievergelt Caroline , Mahata Manjula , Khandrika Srikrishna , Rao Fangwen , Fung Maple M. , Mahata Sushil K. , Hamilton Bruce A. , O'Connor Daniel T. 
Published: January 2014

ABSTRACT

Rationale
Obesity is a heritable trait that contributes to hypertension and subsequent cardiorenal disease risk; thus, the investigation of genetic variation that predisposes individuals to obesity is an important goal. Circulating peptide YY (PYY) is known for its appetite and energy expenditure-regulating properties; linkage and association studies have suggested that PYY genetic variation contributes to susceptibility for obesity, rendering PYY an attractive candidate for study of disease risk.

Design
To explore whether common genetic variation at the human PYY locus influences plasma PYY or metabolic traits, we systematically resequenced the gene for polymorphism discovery and then genotyped common single-nucleotide polymorphisms across the locus in an extensively phenotyped twin sample to determine associations. Finally, we experimentally validated the marker-on-trait associations using PYY 3′-untranslated region (UTR)/reporter and promoter/reporter analyses in neuroendocrine cells.

Results
Four common genetic variants were discovered across the locus, and three were typed in phenotyped twins. Plasma PYY was highly heritable (P &lt; 0.0001), and genetic pleiotropy was noted between plasma PYY and body mass index (BMI) (P = 0.03). A PYY haplotype extending from the proximal promoter (A-23G, rs2070592) to the 3′-UTR (C+1134A, rs162431) predicted not only plasma PYY (P = 0.009) but also other metabolic syndrome traits. Functional studies with transfected luciferase reporters confirmed regulatory roles in altering gene expression for both 3′-UTR C+1134A (P &lt; 0.001) and promoter A-23G (P = 0.0016).

Conclusions
Functional genetic variation at the PYY locus influences multiple heritable metabolic syndrome traits, likely conferring susceptibility to obesity and subsequent cardiorenal disease.
Dual Inhibition of Mitogen-Activated Protein Kinase Kinase and Mammalian Target of Rapamycin in Differentiated and Anaplastic Thyroid Cancer
Authors: Jin Ning , Jiang Tianyun , Rosen D. Marc , Nelkin Barry D. , Ball Douglas W. 
Published: January 2014

ABSTRACT

Context
Differentiated thyroid cancer and anaplastic thyroid cancer tumors frequently have activation of the ras/raf /MAPK kinase (MEK)/ERK and phosphatidylinositol 3-kinase (PI-3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathways.

Objective
The objective of the study was to investigate the efficacy of MEK and mTOR inhibitors in preclinical thyroid cancer treatment models with defined mutation status.

Experimental Design
The MEK inhibitor AZD6244 (ARRY-142886) and mTOR inhibitor rapamycin were tested separately and in combination in 10 differentiated thyroid cancer and anaplastic thyroid cancer cell lines and in a xenograft model for evidence of pathway inhibition, growth inhibition, apoptosis, and long-range adaptation and resistance.

Results
Seven of 10 tested lines had evidence of significant basal activity of the PI-3K/AKT/mTOR pathway, with elevated phosphorylated AKT and phosphorylated p70 S6 kinase. Activation of ras/RAF/MEK/ERK was equally common in this panel. All 10 lines exhibited better than 60% growth inhibition with combined MEK and mTOR inhibition, including lines with BRAF, Ret-PTC, ras, and PTEN mutations. Rapamycin or AZD6244 alone achieved this threshold in six and two lines, respectively. Dual-pathway inhibition in the Ret-PTC mutant cell line TPC1 caused an intense G1 arrest in cell culture and reversible cytostatic inhibition in a xenograft model. We did not observe significant feedback up-regulation of AKT activation in either acute or prolonged exposures.

Conclusion
These preclinical results support the inclusion of thyroid cancer patients in early-phase clinical trials combining ras/RAF/MEK/ERK and PI-3K/AKT/mTOR pathway inhibition.
Effects of Endogenous Growth Differentiation Factor 9 on Activin A-Induced Inhibin B Production in Human Granulosa-Lutein Cells
Authors: Shi Feng-Tao , Cheung Anthony P. , Huang He-Feng , Leung Peter C. K. 
Published: January 2014

ABSTRACT

Background
We recently reported on the effects of exogenous growth differentiation factor 9 (GDF9) in enhancing activin A-induced inhibin βB-subunit mRNA and inhibin B levels in human granulosa-lutein (hGL) cells by modulating key components of the activin signaling pathway. We undertook the following study to characterize the role of endogenous GDF9 in this regard.

Methods
We compared inhibin subunit (α, βA, and βB) mRNA and inhibin B levels and activation of activin receptors (ACVRs) and Smad signaling pathway in hGL cells obtained from women undergoing in vitro fertilization and cultured with and without activin A treatment after GDF9-targeting small interfering RNA transfection. GDF9, inhibin subunits, ACVR2B/1B and Smad2/3/4/7 mRNA and/or protein levels, Smad phosphorylation, and inhibin B were assessed with RT-PCR, immunoblotting, and ELISA. Data were analyzed by ANOVA followed by Tukey’s test.

Results
GDF9 was detected as mRNA and protein in hGL cells and protein in follicular fluid from all 11 patients tested. Reduced endogenous GDF9 expression after targeting small interfering RNA transfection was associated with decreased ACVR2B/1B and Smad2/3/4 but increased inhibitory Smad7 mRNA and protein levels and, consequently, reduced activin A-induced βB-subunit mRNA and inhibin B levels.

Conclusions
We report here for the first time autocrine roles for endogenous GDF9 in hGL cells in enhancing activin A-induced βB-subunit mRNA and inhibin B levels via key components of the activin signaling pathway. However, the relative contributions of GDF9 in granulosa cells vs. oocyte as autocrine/paracrine regulators of βB-subunit and inhibin B production in normal and abnormal human ovarian functions remain to be determined.
Phosphodiesterase 11A (PDE11A) Genetic Variants May Increase Susceptibility to Prostatic Cancer
Authors: Faucz Fabio Rueda , Horvath Anelia , Rothenbuhler Anya , Almeida Madson Q. , Libé Rossella , Raffin-Sanson Marie-Laure , Bertherat Jerome , Carraro Dirce Maria , Soares Fernando Augusto , de Campos Molina Gustavo , Campos Antonio H. , Alexandre Rodrigo B. , Bendhack Marcelo Luiz , Nesterova Maria , Stratakis Constantine A. 
Published: January 2014

Abstract
Context: Among the genomic loci harboring potential candidate genes for prostatic cancer (PCa) is the 2q31-39 chromosomal region that harbors the gene encoding phosphodiesterase 11A (PDE11A). In addition, the combined cancer genome expression metaanalysis datasets included PDE11A among the top 1% down-regulated genes in PCa.
Objective: In the present study, we screened 50 unrelated PCa patients of Brazilian descent for PDE11A coding defects.
Design: The study consisted of sequencing of PDE11A, in vitro functional assays, and immunostaining analysis.
Results: We identified eight different sequence alterations in 15 patients (30%): one stop-codon and seven missense mutations. Three of the variants (R202C, Y658C, and E840K) were novel, and the remaining five (Y727C, R804H, R867G, M878V, and R307X) have been associated with predisposition to adrenal or testicular tumors. The overall prevalence of PDE11A-inactivating sequence variants among PCa patients was significantly higher than in 287 healthy controls (0.16 vs. 0.051, respectively, P &lt; 0.001, odds ratio 3.81, 95% confidence interval 1.86–7.81) and the R202C, Y658C, and E840K substitutions were not found in controls. All missense mutations led to decreased PDE11A activity in human embryonic kidney 293 and PC3M cells and immunostaining of PCa samples with sequence changes showed decreased PDE11A protein expression.
Conclusion: Our data suggest that, like in the adrenal cortex and the testicular germ cells, PDE11A-inactivating genetic alterations may play a role in susceptibility to PCa.
Tumor Necrosis-Like Weak Inducer of Apoptosis as a Proinflammatory Cytokine in Human Adipocyte Cells: Up-Regulation in Severe Obesity Is Mediated by Inflammation But Not Hypoxia
Authors: Vendrell Joan , Maymó-Masip Elsa , Tinahones Francisco , García-España Antonio , Megia Ana , Caubet Enric , García-Fuentes Eduardo , Chacón Matilde R. 
Published: January 2014

abstract
Context: Adipose tissue hypoxia and endoplasmic reticulum (ER) stress may link the presence of chronic inflammation and macrophage infiltration in severely obese subjects. We previously reported the up-regulation of TNF-like weak inducer of apoptosis (TWEAK)/fibroblast growth factor-inducible 14 (Fn14) axis in adipose tissue of severely obese type 2 diabetic subjects.
Objectives: The objective of the study was to examine TWEAK and Fn14 adipose tissue expression in obesity, severe obesity, and type 2 diabetes in relation to hypoxia and ER stress.
Design: In the obesity study, 19 lean, 28 overweight, and 15 obese nondiabetic subjects were studied. In the severe obesity study, 23 severely obese and 35 control subjects were studied. In the type 2 diabetes study, 11 type 2 diabetic and 36 control subjects were studied. The expression levels of the following genes were analyzed in paired samples of sc and visceral adipose tissue: Fn14, TWEAK, VISFATIN, HYOU1, FIAF, HIF-1a, VEGF, GLUT-1, GRP78, and XBP-1. The effect of hypoxia, inflammation, and ER stress on the expression of TWEAK and Fn14 was examined in human adipocyte and macrophage cell lines.
Results: Up-regulation of TWEAK/Fn14 and hypoxia and ER stress surrogate gene expression was observed in sc and visceral adipose tissue only in our severely obese cohort. Hypoxia modulates TWEAK or Fn14 expression in neither adipocytes nor macrophages. On the contrary, inflammation up-regulated TWEAK in macrophages and Fn14 expression in adipocytes. Moreover, TWEAK had a proinflammatory effect in adipocytes mediated by the nuclear factor-κB and ERK but not JNK signaling pathways.
Conclusions: Our data suggest that TWEAK acts as a pro-inflammatory cytokine in the adipose tissue and that inflammation, but not hypoxia, may be behind its up-regulation in severe obesity.
High Performance of Y-doped Sn-Zn-O Films Fabricated by Solution-process for Amorphous Thin Film Transistors
Authors: Yu Yunxuan , Gong Xian , Liu Dong , Wang Yan , Kang Jinfeng 
Published: January 2014

ABSTRACTThe effect of Y dopant incorporated into ZTO with different Y ratios in Y-ZTO system on the performances of ZTO-based TFTs is investigated by using sol-gel process. The proper Y doped ZTO present both high film crystallization temperature and superior electrical properties as an active channel layer of TFTs. The fabricated YZTO-based TFTs with 11% Y show the excellent devices performance such as the channel field effect mobility of 1.756 cm2/Vs, SS of 2.13 V/dec, threshold voltage of 0.8V and on/off ratio of 3.12×106.
Reducing Infections Using Nanotechnology
Authors: Webster Thomas J. 
Published: January 2014

ABSTRACTVentilator associated pneumonia (VAP) is a serious and costly clinical problem. Specifically, receiving mechanical ventilation for over 24 hours increases the risk of VAP and is associated with high morbidity, mortality and medical costs. Cost effective endotracheal tubes (ETTs) that are resistant to bacterial infection could help prevent this problem. The objective of this study was to determine differences in the growth ofStaphylococcus aureus(S. aureus) on nanomodified and unmodified polyvinyl chloride (PVC) ETTs under dynamic airway conditions. PVC ETTs were modified to have nanometer surface features by soaking them inRhizopus arrhisus,a fungal lipase. Twenty-four hour experiments (supported by computational models) showed that air flow conditions within the ETT influenced both the location and concentration of bacterial growth on the ETTs especially within areas of tube curvature. More importantly, experiments revealed a 1.5 log reduction in the total number ofS. aureuson the novel nanomodified ETTs compared to the conventional ETTs after 24 hours of air flow. This dynamic study showed that lipase etching can create nano-rough surface features on PVC ETTs that suppressS. aureusgrowth and, thus, may provide clinicians with an effective and inexpensive tool to combat VAP.
Changing prejudice with evaluative conditioning
Authors: Balas Robert , Sweklej Joanna 
Published: January 2014

AbstractThe presented study investigates attitude change using a cross-modal evaluative conditioning (EC) paradigm. EC is a change in evaluative responses towards initially neutral stimulus (CS) due to its repeated pairing with affectively valenced stimulus (US). A positive scent of instant chocolate (US+) was used together with pictures of homeless people (US-) to change affective responses towards neutral names (CS). We show that a classic EC effect, i.e. more negative CS evaluations after its pairing with negative images of the homeless, can be eliminated when a competitive US, i.e. a positive chocolate scent, is present in the environment. Additionally, the study demonstrates chocolate scent selectively increased attitude towards homeless as measured by perceived distance to self and a self-report questionnaire. Moreover, this effect was not mediated by mood changes. We argue that scents can be used to change attitudes towards stigmatized groups.
Associations Between Death Fascination, Death Anxiety and Religion among Polish College Students
Authors: Lee Sherman A. , Piotrowski Jarosław P. , Różycka Joanna , Żemojtel-Piotrowska Magdalena A. 
Published: January 2014

Abstract
Previous research examining the relationship between religion and attitudes about death have yielded mixed results due to over-simplified conceptualizations of constructs, lack of theory, and an over-reliance on Western samples. To overcome these issues, the present study examined the relationship between three types of religious orientation and two types of death attitudes among a sample of 532 college students in Poland. The results demonstrated unique relations between religion and death attitudes, as well emphasized the importance of considering religious engagement as a moderating variable. Although the results were generally consistent with Terror Management Theory, other theoretical perspectives were considered as well.
COMBING ABILITY OF CMS AND RESTORERS IN RICE (O. sativa L.)
Authors: Biswas P. S. , Julfiquar A. W. , Wazuddin M. 
Published: January 2014

General and specific combining ability effects were estimated from a 5 line × 8 tester crosses to explore the genetic behavior of CMS and restorers in rice. The variance for GCA and SCA showed predominance of non-additive gene action for all the ten morpho-physiological traits. The estimates of GCA effects revealed that none of the parent was general combiner for all the traits in desired direction. Gan46A and BR827R were good general combiners for higher grain yield coupled with earliness, and IR46R and BR168R was good general combiner for grain yield and lateness in maturity. Good x poor general combiners (Gan46A × Gui99R) for grain yield produced the best specific cross for higher grain yield coupled with earliness, longer panicle, panicles/plant, filled grains/panicle and less sterility (%). Additive × additive, additive × dominance and dominance × dominance gene interactions were involved in deriving good specific cross for grain yield.DOI: http://dx.doi.org/10.3329/bjpbg.v20i1.17013