bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrin Activates Receptor-Like Protein Tyrosine Phosphatase α, Src, and Rho to Increase Prolactin Gene Expression through a Final Phosphatidylinositol 3-Kinase/Cytoskeletal Pathway that Is Additive with Insulin
Authors: Vulin Anthony I. , Jacob Kirsten K. , Stanley Frederick M. 
Published: May 2005

AbstractWe previously showed that receptor-like protein tyrosine phosphatase (RPTP)-α inhibited insulin-increased prolactin gene transcription. Others suggested that RPTPα was a key intermediary between integrins and activation of Src. We present evidence that inhibition of insulin-increased prolactin gene transcription was secondary to RPTPα activation of Src, reflecting its role as mediator of integrin responses. Src kinase activity was increased in GH4 cells transiently or stably expressing RPTPα and cells plated on the integrin-α5β1 ligand fibronectin. C-terminal Src kinase inactivated Src and blocked RPTPα inhibition of insulin-increased prolactin gene transcription. Expression of dominant-negative Src also prevented the RPTPα-mediated inhibition of insulin-increased prolactin gene expression. Low levels of a constitutively active Src mutant (SrcY/F) stimulated whereas higher expression levels of Src Y/F inhibited prolactin gene expression. Src-increased prolactin gene transcription was inhibited by expression of a blocking Rho-mutant (RhoN19), suggesting that Src acted through or required active Rho. Experiments with an activated Rho-mutant (RhoL63) demonstrated a biphasic activation/repression of prolactin gene transcription that was similar to the effect of Src. The effects of both Src and Rho were phosphatidylinositol 3-kinase dependent. Expression of SrcY/F or RhoL63 altered the actin cytoskeleton and morphology of GH4 cells. Taken together, these data suggest a physiological pathway from the cell matrix to increased prolactin gene transcription mediated by RPTPα/Src/Rho/phosphatidylinositol 3-kinase and cytoskeletal change that is additive with effects of insulin. Over activation of this pathway, however, caused extreme alteration of the cytoskeleton that blocked activation of the prolactin gene.
Peroxisome Proliferator-Activated Receptor α (PPARα) Potentiates, whereas PPARγ Attenuates, Glucose-Stimulated Insulin Secretion in Pancreatic β-Cells
Authors: Ravnskjaer Kim , Boergesen Michael , Rubi Blanca , Larsen Jan K. , Nielsen Tina , Fridriksson Jakob , Maechler Pierre , Mandrup Susanne 
Published: May 2005

AbstractFatty acids (FAs) are known to be important regulators of insulin secretion from pancreatic β-cells. FA-coenzyme A esters have been shown to directly stimulate the secretion process, whereas long-term exposure of β-cells to FAs compromises glucose-stimulated insulin secretion (GSIS) by mechanisms unknown to date. It has been speculated that some of these long-term effects are mediated by members of the peroxisome proliferator-activated receptor (PPAR) family via an induction of uncoupling protein-2 (UCP2). In this study we show that adenoviral coexpression of PPARα and retinoid X receptor α (RXRα) in INS-1E β-cells synergistically and in a dose- and ligand-dependent manner increases the expression of known PPARα target genes and enhances FA uptake and β-oxidation. In contrast, ectopic expression of PPARγ/RXRα increases FA uptake and deposition as triacylglycerides. Although the expression of PPARα/RXRα leads to the induction of UCP2 mRNA and protein, this is not accompanied by reduced hyperpolarization of the mitochondrial membrane, indicating that under these conditions, increased UCP2 expression is insufficient for dissipation of the mitochondrial proton gradient. Importantly, whereas expression of PPARγ/RXRα attenuates GSIS, the expression of PPARα/RXRα potentiates GSIS in rat islets and INS-1E cells without affecting the mitochondrial membrane potential. These results show a strong subtype specificity of the two PPAR subtypes α and γ on lipid partitioning and insulin secretion when systematically compared in a β-cell context.
Transcriptional Regulation of Dehydroepiandrosterone Sulfotransferase (SULT2A1) by Estrogen-Related Receptor α
Authors: Seely Jeremiah , Amigh Karla Saner , Suzuki Takashi , Mayhew Bobbie , Sasano Hironobu , Giguere Vincent , Laganière Josée , Carr Bruce R. , Rainey William E. 
Published: May 2005

AbstractThe estrogen-related receptors (ERRα, -β, and -γ) are a subfamily of orphan nuclear receptors (designated NR3B1, NR3B2, and NR3B3) that are structurally and functionally related to estrogen receptors α and β. Herein we test the hypothesis that ERRα regulates transcription of the genes encoding the enzymes involved in adrenal steroid production. Real-time RT-PCR was first used to determine the levels of ERRα mRNA in various human tissues. Adult adrenal levels of ERRα transcript were similar to that seen in heart, which is known to highly express ERRα. Expression of ERRα in the adult adrenal was then confirmed using Western blotting and immunohistochemistry. To examine the effects of ERRα on steroidogenic capacity we used reporter constructs with the 5′-flanking regions of steroidogenic acute regulatory protein (StAR), cholesterol side-chain cleavage (CYP11A), 3β-hydroxysteroid dehydrogenase type II (HSD3B2), 17α-hydroxylase/17,20-lyase (CYP17), and dehydroepiandrosterone sulfotransferase (SULT2A1). Cotransfection of these reporter constructs with wild-type ERRα or VP16-ERRα expression vectors demonstrated ERRα enhanced reporter activity driven by flanking DNA from CYP17 and SULT2A1. SULT2A1 promoter activity was most responsive to the ERRα and VP16-ERRα, increasing activity 2.6- and 79.5-fold, respectively. ERRα effects on SULT2A1 were greater than the stimulation seen in response to steroidogenic factor 1 (SF1). Transfection of serial deletions of the 5′-flanking DNA of the SULT2A1 gene and EMSA experiments indicated the presence of three functional regulatory cis-elements which shared sequence similarity to binding sites for SF1. Taken together, the expression of ERRα in the adrenal and its regulation of SULT2A1 suggest an important role for this orphan receptor in the regulation of adrenal steroid production.
Deficiency of the Very Low-Density Lipoprotein (VLDL) Receptors in Streptozotocin-Induced Diabetic Rats: Insulin Dependency of the VLDL Receptor
Authors: Iwasaki Tadao , Takahashi Sadao , Takahashi Masao , Zenimaru Yasuo , Kujiraoka Takeshi , Ishihara Mitsuaki , Nagano Makoto , Suzuki Jinya , Miyamori Isamu , Naiki Hironobu , Sakai Juro , Fujino Takahiro , Miller Norman E. , Yamamoto Tokuo T. , Hattori Hiroaki 
Published: May 2005

AbstractHyperlipidemia is a common feature of diabetes and is related to cardiovascular disease. The very low-density lipoprotein receptor (VLDL-R) is a member of the low-density lipoprotein receptor (LDL-R) family. It binds and internalizes triglyceride-rich lipoproteins with high specificity. We examined the etiology of hyperlipidemia in the insulin-deficient state. VLDL-R expression in heart and skeletal muscle were measured in rats with streptozotocin (STZ)-induced diabetes. STZ rats showed severe hyperlipidemia on d 21 and 28, with a dramatic decline in VLDL-R protein in skeletal muscle (&gt;90%), heart (∼50%) and a loss of adipose tissues itself on d 28. The reduction of VLDL-R protein in skeletal muscle could not be explained simply by a decrease at the transcriptional level, because a dissociation between VLDL-R protein and mRNA expression was observed. The expression of LDL-R and LDL-R-related protein in liver showed no consistent changes. Furthermore, no effect on VLDL-triglyceride production in liver was observed in STZ rats. A decrease in postheparin plasma lipoprotein lipase activity started on d 7 and continued to d 28 at the 50% level even though severe hyperlipidemia was detected only on d 21 and 28. In rat myoblast cells, serum deprivation for 24 h induced a reduction in VLDL-R proteins. Insulin (10−6m), but not IGF-I (10 ng/ml), restored the decreased VLDL-R proteins by serum deprivation. These results suggest that the combination of VLDL-R deficiency and reduced plasma lipoprotein lipase activity may be responsible for severe hyperlipidemia in insulin-deficient diabetes.
Cloning and Characterization of a Functional Type II Gonadotropin-Releasing Hormone Receptor with a Lengthy Carboxy-Terminal Tail from an Ancestral Vertebrate, the Sea Lamprey
Authors: Silver Matthew R. , Nucci Nathaniel V. , Root Adam R. , Reed Karen L. , Sower Stacia A. 
Published: May 2005

AbstractA full-length transcript encoding a functional type II GnRH receptor was cloned from the pituitary of the sea lamprey, Petromyzon marinus. The current study is the first to identify a pituitary GnRH receptor transcript in an agnathan, which is the oldest vertebrate lineage. The cloned receptor retains the conserved structural features and amino acid motifs of other known GnRH receptors and notably includes a C-terminal intracellular tail of approximately 120 amino acids, the longest C-terminal tail of any vertebrate GnRH receptor identified to date. The lamprey GnRH receptor was shown to activate the inositol phosphate (IP) signaling system; stimulation with either lamprey GnRH-I or lamprey GnRH-III led to dose-dependent responses in transiently transfected COS7 cells. Furthermore, analyses of serially truncated lamprey GnRH receptor mutants indicate perturbations of the C-terminal tail disrupts IP accumulation, however, the tailless lamprey GnRH receptor was not only functional but was also capable of stimulating IP levels equal to wild type. Expression of the receptor transcript was demonstrated in the pituitary and testes using RT-PCR, whereas in situ hybridization showed expression and localization of the transcript in the proximal pars distalis of the pituitary. The phylogenetic placement and structural and functional features of this GnRH receptor suggest that it is representative of an ancestral GnRH receptor. In addition to having an important role in lamprey reproductive processes, the extensive C-terminal tail of this lamprey GnRH receptor may have great significance for understanding the evolutionary change of this vital structural feature within the GnRH receptor family.
Hedgehog Signaling in Mouse Ovary: Indian Hedgehog and Desert Hedgehog from Granulosa Cells Induce Target Gene Expression in Developing Theca Cells
Authors: Wijgerde Mark , Ooms Marja , Hoogerbrugge Jos W. , Grootegoed J. Anton 
Published: May 2005

AbstractFollicle development in the mammalian ovary requires interactions among the oocyte, granulosa cells, and theca cells, coordinating gametogenesis and steroidogenesis. Here we show that granulosa cells of growing follicles in mouse ovary act as a source of hedgehog signaling. Expression of Indian hedgehog and desert hedgehog mRNAs initiates in granulosa cells at the primary follicle stage, and we find induced expression of the hedgehog target genes Ptch1 and Gli1, in the surrounding pre-theca cell compartment. Cyclopamine, a highly specific hedgehog signaling antagonist, inhibits this induced expression of target genes in cultured neonatal mouse ovaries. The theca cell compartment remains a target of hedgehog signaling throughout follicle development, showing induced expression of the hedgehog target genes Ptch1, Ptch2, Hip1, and Gli1. In periovulatory follicles, a dynamic synchrony between loss of hedgehog expression and loss of induced target gene expression is observed. Oocytes are unable to respond to hedgehog because they lack expression of the essential signal transducer Smo (smoothened). The present results point to a prominent role of hedgehog signaling in the communication between granulosa cells and developing theca cells.
Progesterone Receptor Isoforms A and B: Temporal and Spatial Differences in Expression during Murine Mammary Gland Development
Authors: Aupperlee Mark D. , Smith Kyle T. , Kariagina Anastasia , Haslam Sandra Z. 
Published: May 2005

Abstract
Progesterone is a potent mitogen in the mammary gland. Based on studies using cells and animals engineered to express progesterone receptor (PR) isoforms A or B, PRA and PRB are believed to have different functions. Using an immunohistochemical approach with antibodies specific for PRA only or PRB only, we show that PRA and PRB expression in mammary epithelial cells is temporally and spatially separated during normal mammary gland development in the BALB/c mouse. In the virgin mammary gland when ductal development is active, the only PR protein isoform expressed was PRA. PRA levels were significantly lower during pregnancy, suggesting a minor role at this stage of development. PRB was abundantly expressed only during pregnancy, during alveologenesis. PRA and PRB colocalization occurred in only a small percentage of cells. During pregnancy there was extensive colocalization of PRB with 5-bromo-2′-deoxyuridine (BrdU) and cyclin D1; 95% of BrdU-positive cells and 83% of cyclin D1-positive cells expressed PRB. No colocalization of PRA with either BrdU or cyclin D1 was observed at pregnancy. In the virgin gland, PRA colocalization with BrdU or cyclin D1 was low; only 27% of BrdU-positive cells and 4% of cyclin D1-positive cells expressed PRA. The implication of these findings is that different actions of progesterone are mediated in PRB positive vs. PRA-positive cells in vivo. The spatial and temporal separation of PR isoform expression in mouse mammary gland provides a unique opportunity to determine the specific functions of PRA vs. PRB in vivo.
Essential Role of the Oocyte in Estrogen Amplification of Follicle-Stimulating Hormone Signaling in Granulosa Cells
Authors: Otsuka Fumio , Moore R. Kelly , Wang Xia , Sharma Shweta , Miyoshi Tomoko , Shimasaki Shunichi 
Published: May 2005

AbstractThe establishment of dominant ovarian follicles that are capable of ovulating fertilizable oocytes is a fundamental determinant of female fertility. This process is governed by pituitary gonadotropins as well as local ovarian factors. Within the follicle, estrogen acts in an autocrine/paracrine manner to enhance FSH action in the granulosa cells. These effects include the augmentation of P450aromatase expression and estradiol production. This feed-forward effect of estrogen is believed to play a key role in follicle dominance. Here we found the essential role of the oocyte in this physiological process using primary cultures of rat granulosa cells. In the presence, but not absence, of oocytes, estrogen amplified FSH-stimulated increases in mRNA expression of P450aromatase, FSH receptor, LH receptor, and inhibin α-, βA-, and βB-subunits as well as cAMP production. Thus, oocytes mediate the estrogen enhancement of FSH action in the granulosa cells. In comparison with FSH, cotreatment with estrogen and oocytes failed to amplify the stimulatory effects of forskolin or 8-bromoadenosine-cAMP on granulosa cell responses including P450aromatase mRNA expression and cAMP production, indicating that estrogen/oocytes amplify FSH action at a site upstream of adenylate cyclase. These findings support the novel conclusion that communication between the oocyte and granulosa cells plays a crucial role in mediating estrogen action during FSH-dependent folliculogenesis.
Myostatin Inhibits Myogenesis and Promotes Adipogenesis in C3H 10T(1/2) Mesenchymal Multipotent Cells
Authors: Artaza Jorge N. , Bhasin Shalender , Magee Thomas R. , Reisz-Porszasz Suzanne , Shen Ruoquin , Groome Nigel P. , Fareez Meerasaluh M. , Gonzalez-Cadavid Nestor F. 
Published: May 2005

AbstractInactivating mutations of the mammalian myostatin gene are associated with increased muscle mass and decreased fat mass; conversely, myostatin transgenic mice that overexpress myostatin in the skeletal muscle have decreased muscle mass and increased fat mass. We investigated the effects of recombinant myostatin protein and antimyostatin antibody on myogenic and adipogenic differentiation of mesenchymal multipotent cells. Accordingly, 10T(1/2) cells were incubated with 5′-azacytidine for 3 d to induce differentiation and then treated with a recombinant protein for myostatin (Mst) carboxy terminal 113 amino acids or a polyclonal anti-Mst antibody for 3, 7, and 14 d. Cells were also cotransfected with a Mst cDNA plasmid expressing the full-length 375-amino acid protein (pcDNA-Mst375) and the silencer RNAs for either Mst (pSil-Mst) or a random sequence (pSil-RS) for 3 or 7 d, and Mst expression was determined. Adipogenesis was evaluated by quantitative image analysis of fat cells before and after oil-red-O staining, immunocytochemistry of adiponectin, and Western blot for CCAAT/enhancer binding protein-α. Myogenesis was estimated by quantitative image analysis-immunocytochemistry for MyoD (Myo differentiation protein), myogenin, and myosin heavy chain type II, or by Western blot for myogenin. 5′-azacytidine-mediated differentiation induced endogenous full-length Mst expression. Recombinant Mst carboxy terminal 113 amino acids inhibited both early and late markers of myogenesis and stimulated both early and late markers of adipogenesis, whereas the antibody against Mst exerted the reverse effects. Myogenin levels at 7 d after transfection of pcDNA-Mst375 were reduced as expected and elevated by pSil-Mst, which blocked efficiently Mst375 expression. In conclusion, myostatin promotes the differentiation of multipotent mesenchymal cells into the adipogenic lineage and inhibits myogenesis.
The Baby Boom and Baby Bust
Authors: Greenwood Jeremy , Seshadri Ananth , Vandenbroucke Guillaume 
Published: May 2005

What caused the baby boom? And can it be explained within the context of the secular decline in fertility that has occurred over the last 200 years? The hypothesis is that: (a) The secular decline in fertility is due to the relentless rise in real wages that increased the opportunity cost of having children; (b) The baby boom is explained by an atypical burst of technological progress in the household sector that occurred in the middle of the last century. This lowered the cost of having children. A model is developed in an attempt to account, quantitatively, for both the baby boom and bust.
Carbon Dioxide Thermal Decomposition: Observation of Incubation
Authors: Oehlschlaeger Matthew A. , Davidson David F. , Jeffries Jay B. , Hanson Ronald K. 
Published: May 2005

Abstract
Incubation prior to the thermal decomposition of CO2 is observed for the first time behind shock waves, confirming the expected bottleneck in collisional activation of this triatomic molecule. The thermal decomposition of carbon dioxide has been investigated behind reflected shock waves at temperatures of 3200–4600 K and pressures of 45–100 kPa. Ultraviolet laser absorption was used to monitor the CO2 concentration with microsecond time resolution, allowing observation of a pronounced incubation period prior to steady CO2 dissociation. Master equation simulations, with a simple model for collisional energy transfer, were carried out to describe the measured incubation times and dissociation rate coefficient. The second order rate coefficient for CO2 dissociation was found to be 3.14 × 1014 exp(−51300 K/T) cm3 mol−1 s−1. The number of incubation collisions was found to range from 7 × 103 at 4600 K to 3.5 × 104 at 3200 K. The master equation simulations suggest that the energy transferred per collision must have a greater than linear dependence on energy.
Combination of Laser- and Mass-Spectroscopic Techniques for the Investigation of Fuel-Rich Flames
Authors: Kohse-Höinghaus Katharina , Schocker Alexander , Kasper Tina , Kamphus Michael , Brockhinke Andreas 
Published: May 2005

Abstract
Soot is one of the most important pollutants originating from combustion. Despite recent advances in the measurement of size and composition of soot particles, their actual formation mechanism is still under debate. It depends on fuel, stoichiometry, temperature, flow conditions and the concentration of a large number of intermediate species. An adequate characterization of this complex reaction system generally requires the use of several complementary techniques.
In this article, we present measurements aiming to study reactions in fuel-rich flames using several complementary techniques. Only with a combination of optical and mass-spectrometric measurements, important features of the early polyaromatic hydrocarbon (PAH) and soot formation chemistry are accessible in detail. Three different techniques are combined to investigate one-dimensional laboratory flames on the same low-pressure burner and their respective merits are discussed: (i) cavity ring-down spectroscopy (CRDS) for the detection of small radicals and measurement of the temperature, (ii) mass spectrometry with electron-impact (EI) ionization in order to measure species with molecular weights up to m/e = 90, and (iii) mass spectrometry with resonantly-enhanced multi-photon ionization (REMPI) to distinguish isomers with masses up to m/e = 178. Measurements of this type may prove a valuable input to improve kinetic and combustion models.
High-Growth-Rate Chemical Vapor Deposition of Silicon: an Experimental and Modeling Approach
Authors: Atakan Burak , Hofstätter Michael , Kohse-Höinghaus Katharina 
Published: May 2005

Abstract
The chemical vapor deposition (CVD) process of silicon from silane has been analyzed by a combined experimental and modeling approach with the aim to optimize growth rate, yield and deposition quality of polycystalline silicon while minimizing gas phase nucleation. The effects of precursor concentration, flow rate and buffer gas have been investigated. Modeling of the gas phase and of the deposition process has been used in a parameter screening to select appropriate deposition conditions in a stagnation-point cold-wall CVD reactor. Deposition experiments have been performed for several silane concentrations with helium, nitrogen and hydrogen as the buffer gases. Polycrystalline films of good quality were obtained with growth rates up to 8 μm/min. The observed trends in the experiments are in good qualitative agreement with model predictions. To achieve high film growth rates and minimal gas phase nucleation, hydrogen is suggested as the diluent gas, potential reasons for this being its involvement in gas phase and surface reactions.
A Composite-Likelihood Approach for Detecting Directional Selection From DNA Sequence Data
Authors: Zhu Lan , Bustamante Carlos D 
Published: May 2005

Abstract
We present a novel composite-likelihood-ratio test (CLRT) for detecting genes and genomic regions that are subject to recurrent natural selection (either positive or negative). The method uses the likelihood functions of Hartl et al. (1994) for inference in a Wright-Fisher genic selection model and corrects for nonindependence among sites by application of coalescent simulations with recombination. Here, we (1) characterize the distribution of the CLRT statistic (Λ) as a function of the population recombination rate (R = 4Ner); (2) explore the effects of bias in estimation of R on the size (type I error) of the CLRT; (3) explore the robustness of the model to population growth, bottlenecks, and migration; (4) explore the power of the CLRT under varying levels of mutation, selection, and recombination; (5) explore the discriminatory power of the test in distinguishing negative selection from population growth; and (6) evaluate the performance of maximum composite-likelihood estimation (MCLE) of the selection coefficient. We find that the test has excellent power to detect weak negative selection and moderate power to detect positive selection. Moreover, the test is quite robust to bias in the estimate of local recombination rate, but not to certain demographic scenarios such as population growth or a recent bottleneck. Last, we demonstrate that the MCLE of the selection parameter has little bias for weak negative selection and has downward bias for positively selected mutations.