bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glucose Controls Cytosolic Ca2+ and Insulin Secretion in Mouse Islets Lacking Adenosine Triphosphate-Sensitive K+ Channels Owing to a Knockout of the Pore-Forming Subunit Kir6.2
Authors: Ravier Magalie A. , Nenquin Myriam , Miki Takashi , Seino Susumu , Henquin Jean-Claude 
Published: September 2008

Glucose-induced insulin secretion is classically attributed to the cooperation of an ATP-sensitive potassium (KATP) channel-dependent Ca2+ influx with a subsequent increase of the cytosolic free Ca2+ concentration ([Ca2+]c) (triggering pathway) and a KATP channel-independent augmentation of secretion without further increase of [Ca2+]c (amplifying pathway). Here, we characterized the effects of glucose in β-cells lacking KATP channels because of a knockout (KO) of the pore-forming subunit Kir6.2. Islets from 1-yr and 2-wk-old Kir6.2KO mice were used freshly after isolation and after 18 h culture to measure glucose effects on [Ca2+]c and insulin secretion. Kir6.2KO islets were insensitive to diazoxide and tolbutamide. In fresh adult Kir6.2KO islets, basal [Ca2+]c and insulin secretion were marginally elevated, and high glucose increased [Ca2+]c only transiently, so that the secretory response was minimal (10% of controls) despite a functioning amplifying pathway (evidenced in 30 mm KCl). Culture in 10 mm glucose increased basal secretion and considerably improved glucose-induced insulin secretion (200% of controls), unexpectedly because of an increase in [Ca2+]c with modulation of [Ca2+]c oscillations. Similar results were obtained in 2-wk-old Kir6.2KO islets. Under selected conditions, high glucose evoked biphasic increases in [Ca2+]c and insulin secretion, by inducing KATP channel-independent depolarization and Ca2+ influx via voltage-dependent Ca2+ channels. In conclusion, Kir6.2KO β-cells down-regulate insulin secretion by maintaining low [Ca2+]c, but culture reveals a glucose-responsive phenotype mainly by increasing [Ca2+]c. The results support models implicating a KATP channel-independent amplifying pathway in glucose-induced insulin secretion, and show that KATP channels are not the only possible transducers of metabolic effects on the triggering Ca2+ signal.Glucose can stimulate insulin secretion from beta cells by increasing Ca2+ influx, cytosolic Ca2+ concentration, and Ca2+ action independently of ATP-sensitive K channels.
Novel Expression of Type 1 Corticotropin-Releasing Hormone Receptor in Multiple Endocrine Cell Types in the Murine Anterior Pituitary
Authors: Westphal Nicole J. , Evans Ryan T. , Seasholtz Audrey F. 
Published: September 2008

The CRH family of ligands signals via two distinct receptors, CRH-R1 and CRH-R2. Previous studies localized CRH-R1 and CRH-R2 to a subset of anterior pituitary corticotropes and gonadotropes, respectively. However, numerous studies have indicated that stress and CRH activity can alter the secretion of multiple anterior pituitary hormones, suggesting a broader expression of the CRH receptors in pituitary. To examine this hypothesis, the in vivo expression of CRH-R1 and CRH-R2 mRNA was further characterized in adult mouse pituitary. Quantitative RT-PCR analysis demonstrated that CRH-R1 mRNA is greater than 100-fold more abundant than CRH-R2 mRNA in male and female mouse pituitaries. Dual in situ hybridization analysis identified cell-specific CRH-R1 expression in the anterior pituitary. At least half of the CRH-R1-positive cells expressed proopiomelanocortin-mRNA (50% in females; 70% in males). In females, a significant percentage of the cells expressing CRH-R1 also expressed transcript for prolactin (40%), LHβ (10%), or TSH (3%), all novel sites of CRH-R1 expression. Similarly in males, a percentage of CRH-R1-positive cells expressed prolactin (12%), LHβ (13%), and TSH (5%). RT-PCR studies with immortalized murine anterior pituitary cell lines showed CRH-R1 and/or CRH-R2 expression in corticotropes (AtT-20 cells), gonadotropes (αT3-1 and LβT2 cells), and thyrotropes (αTSH cells). Whereas CRH-R1 expression in corticotropes is well established, the presence of CRH-R1 mRNA in a subset of lactotropes, gonadotropes, and thyrotropes establishes these cell types as novel sites of murine CRH-R1 expression and highlights the pituitary as an important site of interaction between the hypothalamus-pituitary-adrenal and multiple endocrine axes.Corticotropin-releasing hormone receptor 1 mRNA is detected in multiple mouse anterior pituitary cell types, including corticotropes, lactotropes, and gonadotropes, in a sexually dimorphic pattern.
Argonaute-2 Expression Is Regulated by Epidermal Growth Factor Receptor and Mitogen-Activated Protein Kinase Signaling and Correlates with a Transformed Phenotype in Breast Cancer Cells
Authors: Adams Brian D. , Claffey Kevin P. , White Bruce A. 
Published: September 2008

Argonaute (Ago) 2 is the catalytic engine of mammalian RNA interference, but little is known concerning the regulation of Ago2 by cell-signaling pathways. In this study we show that expression of Ago2, but not Ago1, Ago3, or Ago4, is elevated in estrogen receptor (ER) α-negative (ERα−) vs. ERα-positive (ERα+) breast cancer cell lines, and in ERα− breast tumors. In MCF-7 cells the low level of Ago2 was found to be dependent upon active ERα/estrogen signaling. Interestingly, the high expression of Ago2 in ERα− cells was severely blunted by inhibition of the epidermal growth factor (EGF) receptor/MAPK signaling pathway, using either a pharmacological MAPK kinase inhibitor, U0126, or a small interfering RNA directed against EGF receptor. Half-life studies using cycloheximide indicated that EGF enhanced, whereas U0126 decreased, Ago2 protein stability. Furthermore, a proteosome inhibitor, MG132, blocked Ago2 protein turnover. The functional consequences of elevated Ago2 levels were examined by stable transfection of ERα+ MCF-7 cells with full-length and truncated forms of Ago2. The full-length Ago2 transfectants displayed enhanced proliferation, reduced cell-cell adhesion, and increased migratory ability, as shown by proliferation, homotypic aggregation, and wound healing assays, respectively. Overexpression of full-length Ago2, but not truncated forms of Ago2 or an empty vector control, reduced the levels of E-cadherin, β-catenin, and β-actin, as well as enhanced endogenous miR-206 activity. These data indicate that Ago2 is regulated at both the transcriptional and posttranslational level, and also implicate Ago2 and enhanced micro-RNA activity in the tumorigenic progression of breast cancer cell lines.
Argonaute-2 is elevated in ERα- breast cancer cells due to epidermal growth factor receptor/MAPK signaling, and overexpression of this gene induces a more transformed phenotype in ERα+ MCF-7 cells.
Target Gene-Specific Regulation of Androgen Receptor Activity by p42/p44 Mitogen-Activated Protein Kinase
Authors: Agoulnik Irina U. , Bingman William E. , Nakka Manjula , Li Wei , Wang Qianben , Liu X. Shirley , Brown Myles , Nancy L. Nancy L. 
Published: September 2008

Abstract
Evidence that the androgen receptor (AR) is not only important in androgen-dependent prostate cancer, but also continues to play a role in tumors that become resistant to androgen deprivation therapies, highlights the need to find alternate means to block AR activity. AR, a hormone-activated transcription factor, and its coactivators are phosphoproteins. Thus, we sought to determine whether inhibition of specific cell signaling pathways would reduce AR function. We found that short-term inhibition of p42/p44 MAPK activity either by a MAPK kinase inhibitor, U0126, or by depletion of kinase with small interfering RNA caused target gene-specific reductions in AR activity. AR enhances histone H3 acetylation of target genes that are sensitive to U0126 including prostate-specific antigen and TMPRSS2, but does not increase histone H3 acetylation of the U0126-resistant PMEPA1 gene. Thus, although AR induces transcription of many target genes, the molecular changes induced by AR at the chromatin level are target gene specific. Long-term treatment (24–48 h) with U0126 causes a G1 cell cycle arrest and reduces AR expression both through a decrease in AR mRNA and a reduction in AR protein stability. Thus, treatments that reduce p42/p44 MAPK activity in prostate cancer have the potential to reduce AR activity through a reduction in expression levels as well as by target gene-selective inhibition of AR function.
The Expression of GPIHBP1, an Endothelial Cell Binding Site for Lipoprotein Lipase and Chylomicrons, Is Induced by Peroxisome Proliferator-Activated Receptor-γ
Authors: Davies Brandon S. J. , Waki Hironori , Beigneux Anne P. , Farber Emily , Weinstein Michael M. , Wilpitz Damien C. , Tai Li-Jung , Evans Ronald M. , Fong Loren G. , Tontonoz Peter , Young Stephen G. 
Published: September 2008

AbstractGlycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1), a protein in the lymphocyte antigen 6 (Ly-6) family, plays a key role in the lipolytic processing of triglyceride-rich lipoproteins. GPIHBP1 binds lipoprotein lipase and chylomicrons and is expressed along the luminal surface of microvascular endothelial cells. Lipolysis is known to be regulated by metabolic factors and is controlled at multiple levels, including the number of LPL binding sites on capillaries. Here, we tested the possibility that GPIHBP1 expression could be regulated by dietary perturbations and by peroxisome proliferator-activated receptors (PPARs). Gpihbp1 transcript levels in the heart and in brown and white adipose tissue increased with fasting and returned toward baseline after refeeding. A PPARγ agonist increased Gpihbp1 expression in adipose tissue, heart, and skeletal muscle, whereas PPARα and PPARδ agonists had no effect. Gpihbp1 was expressed in endothelial cells of embryoid bodies generated from mouse embryonic stem cells, and Gpihbp1 expression in embryoid bodies was up-regulated by a PPARγ agonist. Sequences upstream from exon 1 of Gpihbp1 contain a strong PPAR binding site, and that site exhibited activity in a luciferase reporter assay. Gpihbp1 transcript levels in brown and white adipose tissue were lower in endothelial cell PPARγ knockout mice than in littermate control mice, suggesting that PPARγ regulates Gpihbp1 expression in vivo. We conclude that GPIHBP1 is regulated by dietary factors and by PPARγ.
Axl and Tyro3 Modulate Female Reproduction by Influencing Gonadotropin-Releasing Hormone Neuron Survival and Migration
Authors: Pierce Angela , Bliesner Brian , Xu Mei , Nielsen-Preiss Sheila , Lemke Greg , Tobet Stuart , Wierman Margaret E. 
Published: September 2008

AbstractGnRH neurons must undergo a complex and precise pattern of neuronal migration to appropriately target their projections to the median eminence to trigger gonadotropin secretion and thereby control reproduction. Using NLT GnRH cells as a model of early GnRH neuronal development, we identified the potential importance of Axl and Tyro3, members of the TAM (Tyro3, Axl, and Mer) family of receptor tyrosine kinases in GnRH neuronal cell survival and migration. Silencing studies evaluated the role of Tyro3 and Axl in NLT GnRH neuronal cells and suggest that both play a role in Gas6 stimulation of GnRH neuronal survival and migration. Analysis of mice null for both Axl and Tyro3 showed normal onset of vaginal opening but delayed first estrus and persistently abnormal estrous cyclicity compared with wild-type controls. Analysis of GnRH neuronal numbers and positioning in the adult revealed a total loss of 24% of the neuronal network that was more striking (34%) when considered within specific anatomical compartments, with the largest deficit surrounding the organum vasculosum of the lamina terminalis. Analysis of GnRH neurons during embryogenesis identified a striking loss of immunoreactive cells within the context of the ventral forebrain compartment (36%) and not more rostrally. Studies using caspase 3 cleavage as a marker of apoptosis showed that Axl−/−, Tyro3−/− double-knockout mice had increased cell death in the nose and dorsal forebrain, supporting the underlying mechanism of cell loss. Together these data suggest that Axl and Tyro3 mediate the survival and appropriate targeting of GnRH neurons to the ventral forebrain, thereby contributing to normal reproductive function and cyclicity in the female.
Nuclear Waste Management at the Interface of Science and Policy: The Canadian Experience
Authors: Leiss William 
Published: September 2008

This paper reviews briefly the history of Canada's civilian nuclear energy program and the consideration of the problem of long-term disposal of nuclear waste. It shows that, after a period of twenty years of initial official deliberations on this problem, the decision making process foundered in the face of a specific dilemma: how to include, within an integrated assessment framework, both “technical” (expert judgment) and “social” (public acceptability) considerations. It argues that an expanded risk management framework, illustrated below, now provides such a framework: The remainder of the paper reviews and comments on a decision making exercise, carried out in Canada in the year 2004, and using a method known as multi-attribute utility analysis (MAU), that provided a new approach to the issue of the management of nuclear waste. It argues that the MAU method has some distinctive advantages, over earlier approaches, where intrinsically controversial risk management situations are concerned.
Structural Analysis as Driver in Surface-Based Design Approaches
Authors: Schein Markus , Tessmann Oliver 
Published: September 2008

This research argues for novel strategies to integrate structural analysis data in architectural design. Instead of a linear procedure of analysis, synthesis, evaluation and post-rationalization a synthesis/evaluation loop is installed which embeds structural analysis data as design driver from early on. The approach regards structural performance as one design criteria within a network of different requirements. An equilibrium of multiple parameters is aspired to instead of a single-parameter-optimum. The research is conducted via a custom-made digital interface between 3d modelling software and an application for structural analysis of space frames. The information exchange provides the basis for successive strategies within a collaborative design process of spatial roof structures: negotiation of an overall form and a multi-dimensional improvement of space frame topologies by a Genetic Algorithm (GA).
The role of attention and immediate memory in vulnerability to interpersonal criticism during family transactions in schizophrenia
Authors: Kéri Szabolcs , Kelemen Oguz 
Published: September 2008

ObjectiveCognitive dysfunctions may represent vulnerability markers to psychosocial stress in schizophrenia. The purpose of this study was to investigate the possibility that cognitive deficits are associated with the emergence of unusual thoughts during a stressful family transaction.MethodsThe cognitive performance of 80 patients with schizophrenia was characterized by the five index scores of the repeatable brief assessment of neuropsychological status (RBANS) test battery (immediate and delayed memory, visuospatial/constructional functions, language, and attention). The patients and one of their family members participated in a 20‐minute interaction during which the number of relatives' harsh criticisms and the number of patients' unusual thoughts was measured.ResultsRegression analyses revealed that criticism together with attention/immediate memory best predicted the number of unusual thoughts (>25% of variance). In patients with poor attention/immediate memory, there was a significant positive relationship between the number of criticisms and unusual thoughts.ConclusionsThe results indicate that family criticism is related to thinking disturbances in patients with poor attention/immediate memory. The enhancement of these cognitive functions may increase resistance to psychosocial stress in schizophrenia.
TaqMan-Based Real-Time PCR for Genotyping Common Polymorphisms of Haptoglobin (HP1 and HP2)
Authors: Soejima Mikiko , Koda Yoshiro 
Published: September 2008

AbstractBackground: The haptoglobin gene (HP) has 2 common codominant alleles (HP1 and HP2) that account for 3 phenotypes. HP2 is generated by a 1.7-kb intragenic duplication of HP1.Methods: We used the real-time TaqMan PCR system to develop an effective method for HP genotyping that allows us to evaluate the relative number of copies of the HP2 allele–specific junctional region of the 1.7-kb gene duplication (HP2) by comparing the intensity of the amplification signals to those of the HP promoter region (HP5′), which was used as the internal control. The difference in threshold cycles (ΔCt) between HP2 and HP5′ was used to assess HP2 copy number. In addition, the assay detects the HP deletion (HPdel) at the same time.Results: The mean 2−ΔΔCt values (the HP2/HP5′ ratio) obtained from 123 samples of known HP genotypes clearly differentiated 2 nonoverlapping intervals that correspond to the HP genotypes. Ratios for HP2/HP1 samples ranged from 0.34–0.50, HP2/HP2 samples ranged from 0.79–0.98, and the absence of an HP2 allele signal was defined as HP1/HP1. We simultaneously detected HPdel. The assay produces results in &lt;1 h.Conclusions: The TaqMan-based real-time PCR method was successfully applied to HP genotyping. The method is easy to use in a molecular diagnosis laboratory, and its robustness and rapidity make it suitable for high-throughput analysis of large populations.
Canadian Evidence on the Constructive Capitalization of Operating Leases*
Authors: Durocher Sylvain 
Published: September 2008

ABSTRACTOne type of relevant ex ante research supporting the accounting standard‐setting process is the study of a proposed standard's impact on reported figures. The International Accounting Standards Board recently decided to review the lease accounting standard, which will naturally involve consideration of the G4 + 1 recommendation to capitalize all noncancellable lease contracts, including operating leases. National evidence of the impact of the G4 + 1 proposals provides feedback for the international standard‐setter. This study developed and used a refined constructive capitalization method, in which company‐specific assumptions — interest rate, total/expired/remaining lives of leased assets, and tax rate — were used to compute the impact of operating‐lease capitalization on key financial indicators for a sample of Canadian public companies. The results indicate that capitalizing operating leases would lead to the recognition of important additional assets and liabilities on the balance sheet. It would therefore significantly increase the debt‐to‐asset ratio and significantly decrease the current ratio. These results were noted across all industry segments in the sample. Income statement effects were generally less material. Significant impacts on return on assets, return on equity, and / or earnings per share were noted in only three industry segments: merchandising and lodging, oil and gas, and financial services. Intercompany comparability would not be affected overall nor within industries, because of similar rankings for each financial indicator before and after operating‐lease capitalization.
Reference ranges for neuroprotein S-100B: from infants to adolescents
Authors: Castellani Christoph , Stojakovic Tatjana , Cichocki Martin , Scharnagl Hubert , Erwa Wolfgang , Gutmann Anton , Weinberg Annelie-Martina 
Published: September 2008

Abstract: Diagnosis and treatment of mild traumatic brain injuries in children are especially problematic. At present, computed tomography (CT) is the standard method to identify if patients with intracranial lesions require inpatient monitoring. CT, however, involves exposure to high doses of X-rays, which should be avoided if possible. In adults, the serum level of neuroprotein S-100B has already been proven to be effective for the selection of patients requiring CT. The aim of the present study was to determine reference ranges for serum S-100B in a large number of healthy children.: All patients younger than 18 years with no recent history of head injuries presenting for routine operations were included in the study.: A total of 394 patients were evaluated. In children from 3 to 18 years an upper reference level of 0.16 μg/L was determined. There was a strong inverse relation between age and S-100B in patients younger than 3 years. As the values in this age group were scattered and the number of cases limited (n=65), no reference range could be calculated.: This study provides S-100B reference ranges for pediatric patients based on the largest group of healthy pediatric patients yet analyzed.Clin Chem Lab Med 2008;46:1296–9.
Ribosomal DNA intergenic spacer of indoor wood-decay fungi
Authors: Schmidt Olaf , Moreth Ute 
Published: September 2008

Abstract
Indoor wood-decay fungi are economically very important. Approximately half of the total damage caused by indoor fungi in Germany is caused by species of the Coniophoraceae. The sequence of the intergenic spacer (IGS) region of the ribosomal DNA was elucidated with the following fungi of this family: Serpula lacrymans (true dry rot fungus), S. himantioides (wild merulius), Meruliporia incrassata (North American dry rot fungus), Leuco-gyrophana pinastri (mine dry rot fungus), Coniophora puteana (brown cellar fungus), and C. marmorata (marmoreus cellar fungus). The IGS length ranges between 2584 and 3785 bp and consists of the short IGS 1 (253–440 bp), the 5S rDNA (118 bp) and the long IGS 2 (2193–3310 bp). IGS 1 is phylogenetically less informative for the investigated Coniophoraceae species. 5S rDNA is transcribed in the reverse direction. IGS 2 contains extended repeat blocks of copies of different length. Intraspecific length polymorphism as a result of different copy number occurs in M. incrassata and L. pinastri. In combination with previous results, the full-length sequence of the rDNA repeat unit is available for important indoor wood-decay fungi. The various rDNA regions can now be used for future identification of unknown sequences by BLAST and also for phylogenetic studies.
Formation of the crystal structure of Lyocell fiber during drying 2nd ICC 2007, Tokyo, Japan, October 25–29, 2007
Authors: Wei Mengyuan , Yang Gesheng , Tian Yaoxin , Shao Huili , Hu Xuechao 
Published: September 2008

Abstract
Lyocell fiber, a new type of regenerated cellulose fiber, is produced by an environmentally friendly dry-wet spinning process without hazardous byproducts. In order to prepare high performance Lyocell fiber, the formation of crystal structure of never dried (n.d.) Lyocell fiber and the difference of crystal structures between n.d. Lyocell fiber and rewetted Lyocell fiber was investigated by wide angle X-ray diffractometry. The results showed that the supramolecular order of n.d. Lyocell fiber with high water content was not fully developed and, accordingly, the paracrystalline moiety of the of fibers was very high. The crystallinity and lateral order increased with the decreasing water content. When water content of n.d. Lyocell fiber was less than 35%, most paracrystalline structures in the fiber turned into crystalline structures. On the other hand, it was found that once the crystal structure of Lyocell fiber was formed, it could not be destroyed by rewetting. This finding indicates that only the crystal structure of Lyocell fiber could be changed. By heat treatment of n.d. Lyocell fiber, the mechanical properties of the fiber were improved effectively.