bluuebunny/crossref_metadata_2025 huggingface dataset:
Processing Reflexives and Pronouns in Picture Noun Phrase
Authors: Runner Jeffrey T. , Sussman Rachel S. , Tanenhaus Michael K.
Published: April 2006

Binding theory (e.g., Chomsky, 1981) has played a central role in both syntactic theory and models of language processing. Its constraints are designed to predict that the referential domains of pronouns and reflexives are nonoverlapping, that is, are complementary; these constraints are also thought to play a role in online reference resolution. The predictions of binding theory and its role in sentence processing were tested in four experiments that monitored participants' eye movements as they followed spoken instructions to have a doll touch a picture belonging to another doll. The instructions used pronouns and reflexives embedded in picture noun phrases (PNPs) containing possessor phrases (e.g., Pick up Ken. Have Ken touch Harry's picture of himself). Although the interpretations assigned to pronouns were generally consistent with binding theory, reflexives were frequently assigned interpretations that violated binding theory. In addition, the timing and pattern of eye movements were inconsistent with models of language processing that assume that binding theory acts as an early filter to restrict the referential domain. The interpretations assigned to reflexives in PNPs with possessors suggest that they are binding‐theory‐exempt logophors, a conclusion that unifies the treatment of reflexives in PNPs.
Glucose Induces Glucagon Release Pulses Antisynchronous with Insulin and Sensitive to Purinoceptor Inhibition
Authors: Grapengiesser Eva , Salehi Albert , Qader Saleem S. , Hellman Bo
Published: April 2006

Both increase of the glucose concentration and activation of purinoceptors are known to affect pancreatic α-cells. Effects obtained with various purino derivatives at 2.8 and 8.3 mmol/liter glucose have been taken to indicate that external ATP is less potent than adenosine as a stimulator of glucagon release. However, when making a corresponding comparison at 20 mmol/liter glucose, we observed marked stimulation of glucagon release from isolated rat islets with 100 μmol/liter adenosine-5-O-2-thiodiphosphate but inhibition with 10 μmol/liter adenosine. Analyses of 30-sec samples of perfusate from rat pancreas indicated that a rise of the glucose concentration from 3 to 20 mmol/liter rapidly induces a glucagon peak followed by regular 4- to 5-min pulses. The glucagon pulses preceded those of insulin with a phase shift (1.8 ± 0.1 min) near half the interpeak interval. Because of the antisynchrony, the maximal glucagon effect on liver cells will be manifested during periods with low concentrations of insulin. In support for the idea that neural P2Y1 receptors are important for coordinating the secretory activity of the islets, both the insulin and glucagon pulses disappeared in the presence of the purinoceptor inhibitor MRS 2179 (10 μmol/liter). However, in contrast to what was observed for insulin, MRS 2179 lowered average glucagon release to the level of the oscillatory nadirs.
Contribution of Multidrug Resistance Protein MRP5 in Control of Cyclic Guanosine 5′-Monophosphate Intracellular Signaling in Anterior Pituitary Cells
Authors: Andric Silvana A. , Kostic Tatjana S. , Stojilkovic Stanko S.
Published: April 2006

The energy-dependent cyclic nucleotide cellular efflux is operative in numerous eukaryotic cells and could be mediated by multidrug resistance proteins MRP4, MRP5, and MRP8. In pituitary cells, however, the operation of export pumps and their contribution to the control of intracellular cyclic nucleotide levels were not studied previously. Here we show that cellular efflux of cyclic nucleotides was detectable in normal and immortalized GH3 pituitary cells under resting conditions and was enlarged after concurrent stimulation of cAMP and cGMP production with GHRH, corticotropin-releasing factor, vasoactive intestinal peptide, pituitary adenylate cyclase-activating polypeptide, and forskolin. In resting and stimulated cells, the efflux pumps transported the majority of de novo-produced cGMP, limiting its intracellular accumulation in a concentration range of 1–2 μm. In contrast, only a small fraction of cAMP was released and there was a time- and concentration-dependent accumulation of this messenger in the cytosol, ranging from 1–100 μm. Stimulation and inhibition of cGMP production alone did not affect cAMP efflux, suggesting the operation of two different transport pathways in pituitary cells. The rates of cAMP and cGMP effluxes were comparable, and both pathways were blocked by probenecid and progesterone. Pituitary cells expressed mRNA transcripts for MRP4, MRP5, and MRP8, whereas GH3 cells expressed only transcripts for MRP5. Down-regulation of MRP5 expression in GH3 cells decreased cGMP release without affecting cAMP efflux. These results indicate that cyclic nucleotide cellular efflux plays a critical role in elimination of intracellular cGMP but not cAMP in pituitary cells and that such selectivity is achieved by expression of MRP5.
C–H Bond Activation by Ruthenium(0) Complexes. Isolation of an Active Intermediate in the Ruthenium Catalyzed Aldol and Michael Reactions
Authors: Mizuho Yuji , Kasuga Noriko , Komiya Sanshiro
Published: April 2006

Carbon-hydrogen bond oxidative addition of alkyl cyanoacetate to Ru(C2H4)(PPh3)3 in benzene at room temperature gives mer-RuH(NCCHCOOR)(NCCH2COOR)(PPh3)3 (R = Me, Et) accompanied by the liberation of ethylene. X-Ray structure analysis of the THF adduct (R = Me) reveals that NCCHCOOMe group bonds to ruthenium not through the methine carbon but the cyano group. These complexes react with benzaldehyde and methyl iodide to give alkyl (E)-1-cyanocinnamate and alkyl 2-cyanopropionate, respectively.
Sulfate-promoted Metal Oxide Catalysts for the Selective Reduction of Nitrogen Monoxide by Propane in Oxygen-rich Atmosphere
Authors: Hamada Hideaki , Kintaichi Yoshiaki , Tabata Mitsunori , Sasaki Motoi , Ito Takehiko
Published: April 2006

The effect of pretreatment with sulfuric acid on several metal oxide catalysts for the title reaction was investigated. TiO2, ZrO2, and Fe2O3 Pretreated with sulfuric acid showed high activity, whereas the activity of Al2O3 was decreased by the treatment.
Lanthanide Trifluoromethanesulfonates as Stable Lewis Acids in Aqueous Media. Yb(OTf)3 Catalyzed Hydroxymethylation Reaction of Silyl Enol Ethers with Commercial Formaldehyde Solution
Authors: Kobayashi Shu
Published: April 2006

Silyl enol ethers smoothly react with commercial formaldehyde solution to give the corresponding hydroxymethylated adducts in high yields by the promotion of a catalytic amount of ytterbium(III) triflate (Yb(OTf)3), which is a stable Lewis acid in aqueous media. Other lanthanide triflates are also found to be effective.
A Novel Thermal Addition of Diaryl Diselenides to Acetylenes
Authors: Ogawa Akiya , Takami Noriaki , Sekiguchi Masahito , Yokoyama Hiroshi , Kuniyasu Hitoshi , Ryu Ilhyong , Sonoda Noboru
Published: April 2006

When diphenyl diselenide is heated at 150–180 °C in the presence of acetylenes, an acetylene insertion reaction into the Se–Se bond of the diselenide takes place to provide vic-bis(phenylseleno)alkenes in moderate to high yields.
Hydrogenation of Carbon Dioxide to Methanol by Lanthana-Supported Palladium Catalyst
Authors: Fan Li , Fujimoto Kaoru
Published: April 2006

Pd/La2O3 catalyst reduced by flowing hydrogen at 500 °C for 1 h was found to be a promising catalyst for hydrogenation of CO2 to methanol. At 230 °C and 30 bar, the CO2 conversion was 4.8% while methanol selectivity reached 82.7% with extremely high durability, even if the composition of reactant gas was CO2 : H2 = 1 : 3.
Enantioselective Cyclopropanation of Allylic Alcohols Catalyzed by a Chiral Disulfonamide-Aluminum Complex
Authors: Imai Nobuyuki , Takahashi Hideyo , Kobayashi Susumu
Published: April 2006

A chiral disulfonamide-alkylaluminum complex prepared from (1R,2R)-N,N′-bis(benzenesulfonyl)-1,2-cyclohexanediamine and trialkylaluminum or i-Bu2AlH has been found to catalyze a Simmons-Smith cyclopropanation of allylic alcohols with Et2Zn and CH2I2 to afford the corresponding cyclopropanes in excellent yields with high enantiomeric excesses.
Pyranylidenemethyl- and Thiopyranylidenemethyl-substituted Furans, Thiophenes, and N-Methylpyrroles as Precursors of Organic Metals and Third-order Nonlinear Optical Materials
Authors: Takimiya Kazuo , Otsubo Tetsuo , Ogura Fumio , Ashitaka Hidetomo , Morita Kazuhiro , Suehiro Tsutomu
Published: April 2006

The title heteroaromatics have been synthesized by Wittig-Hornor reactions of the appropriate heterocyclic dialdehydes with diethyl pyranyl- and thiopyranyl-phosphonate. Cyclic voltammetry indicated their strong π-donor abilities, and some TCNQ complexes showed high electrical conductivities. They were also found to have large third-order nonlinear optical susceptibilities.
Conversion of 1-(ω-Alkynyl)-1,2-propadienyl Sulfides to Bicyclic Dienones by the Use of Iron Carbonyl Complex
Authors: Narasaka Koichi , Shibata Takanori
Published: April 2006

1-(ω-Alkenyl)-1,2-propadienyl sulfide reacts with Fe(CO)4(NMe3) under photo irradiation conditions and a cyclized and carbonylated η3-allyl mononuclear iron complex is isolated. On the other hand, the reaction of 1-(ω-alkynyl)-1,2-propadienyl sulfides and Fe(CO)4(NMe3) also proceeds by photo irradiation to give various bicyclic dienones through the η3-allyl iron complex.
Alternating Molecular Arrangements in Paired Bilayers of Oppositely Charged Amphiphiles
Authors: Nishimi Taisei , Tachikawa Masami , Maeda Tadashi , Ishikawa Yuichi , Kunitake Toyoki
Published: April 2006

Equimolar mixtures of cyclam amphiphiles and malonate amphiphiles produced uniformly paired bilayers. Absorption spectra and X-ray diffraction measurements showed that molecular alignments were determined by combinations of the alkyl chain length of paired bilayer components as in the respective single-component bilayers.
H2S and CH3SH Sensor Using a Thick Film of Gold-Loaded Tungsten Oxide
Authors: Ando Masami , Suto Seiichi , Suzuki Takahiro , Tsuchida Takashi , Nakayama Chiaki , Miura Norio , Yamazoe Noboru
Published: April 2006

A thick film sensor element fabricated with 0.5 wt% Au-loaded WO3 was found to exhibit excellent sensing properties to H2S and CH3SH in air at 300 °C. The element was sensitive to very dilute H2S and CH3SH, the detection limits of the gases being 20 ppb and 30 ppb, respectively.
Electroenzymatic Oxidation of Alcohols on a Poly(acrylic acid)-coated Graphite Felt Electrode Terimmobilizing Ferrocene, Diaphorase and Alcohol Dehydrogenase
Authors: Osa Tetsuo , Kashiwagi Yoshitomo , Yanagisawa Yoshinori
Published: April 2006

A preparative electroenzymatic oxidation of alcohols was successfully carried out on a poly(acrylic acid)-coated graphite felt electrode ter-immobilizing ferrocene, diaphorase and alcohol dehydrogenase in the domain of the poly(acrylic acid) layer in a 1 mM NADH / phosphate buffer (pH 7.2) with high stereoselectivity ( >96%), high isolated yield ( >90%) and high current efficiency ( >89%).
Total Synthesis of a Novel β-Glucosidase Inhibitor, Cyclophellitol Starting from d-Glucose
Authors: Sato Ken-ichi , Bokura Masayuki , Moriyama Hironori , Igarashi Tetsutaro
Published: April 2006

Cyclophellitol [1l-(1,2,4,6/3,5)-1,2-anhydro-6-(hydroxymethyl)-cyclohexane-1,2,3,4,5-pentol], a novel β-glucosidase inhibitor, has been synthesized from d-glucose via a branched-chain 6-deoxyhex-5-enopyranoside.
Enhanced Reducing Ability by the Combination of SmI2 and Sm Metal in the Reduction of Alkyl Halides
Authors: Ogawa Akiya , Nanke Taizoh , Takami Noriaki , Sumino Yukihito , Ryu Ilhyong , Sonoda Noboru
Published: April 2006

Reduction of alkyl bromides and iodides easily takes place under mild conditions by the use of a reaction system combining SmI2 with Sm metal. The reducing ability of this Sm/SmI2 mixed reagent is superior to that of SmI2 or Sm metal used independently.
Synthesis and Structure of Novel Hexanuclear Iron(III) Complexes with μ-Hydroxo-bis(μ-amino acid-O,O′)diiron Cores
Authors: Tokii Tadashi , Ide Kouji , Nakashima Michio , Koikawa Masayuki
Published: April 2006

Novel hexanuclear iron(III) complexes with Fe2(μ-OH)(μ-RCOO)2 moiety in the molecule (where RCOO is an amphoteric ion of β-alanine (1) or glycylglycine) have been prepared. The crystal structure of 1 consists of two μ-hydroxo-bis(μ-β-alanine-O,O′)diiron(III) cores and two iron(III) ions bridged by μ-oxo ions at each iron(III) site in the cores.
N-Alkyl lmidazoles as Effective Axial Ligands in the Aerobic Asymmetric Epoxidation of Unfunctionalized Olefins Catalyzed by Optically Active Manganese(III)-salen-type Complex
Authors: Imagawa Kiyomi , Nagata Takushi , Yamada Tohru , Mukaiyama Teruaki
Published: April 2006

N-Alkyl imidazoles are effective axial ligands to achieve highly enantioselective epoxidation of unfunctionalized olefins by combined use of molecular oxygen and pivalaldehyde with optically active Mn(III)-salen-type complex catalysts. In the presence of N-alkyl imidazole, the epoxidation of 2,2-dimethylchromene proceeded smoothly to afford the corresponding optically active epoxide in 92% enantiomeric excess.
Enantioselective Aldolation Mediated by Functionalized Bilayer Membranes as Artificial Vitamin B6-dependent Enzymes
Authors: Murakami Yukito , Kikuchi Jun-ichi , Miyajima Tetsuya , Hisaeda Yoshio
Published: April 2006

Supramolecular bilayer assemblies, each composed of a peptide lipid having an (S)-alanine residue, an additional one having (S)-binaphthol and (S)-alanine moieties, a hydrophobic pyridoxal derivative, and copper(II) ions, mediated the aldolation of glycine with benzaldehyde to afford ß-phenylserine under mild reaction conditions, exhibiting marked enantioselectivity.
CO2 Hydrogenation for C2+ Alcohols Synthesis over Silica-Supported Ir-Mo Catalysts
Authors: Kishida Masahiro , Yamada Keiki , Nagata Hideo , Wakabayashi Katsuhiko
Published: April 2006

CO2 hydrogenation over silica-supported catalysts was carried out to investigate the synthesis of C2+ alcohols (ethanol, propanol and butanol). The Ir-Mo bimetallic system among the catalysts investigated was found to produce C2+ alcohols. The catalytic performance of the Ir-Mo catalysts was examined as a function of Mo/Ir molar ratio. It was revealed that the highest selectivity to C2+ alcohols was obtained in the Mo/Ir ratios of around 0.3.
An NMR Study of Chiral Recognition Relevant to the Liquid Chromatographic Separation of Enantiomers by a Cellulose Derivative
Authors: Yashima Eiji , Yamada Makiko , Okamoto Yoshio
Published: April 2006

Chiral discrimination of enantiomers by cellulose tris(4-trimethylsilylphenylcarbamate) (CTSP) was studied by 1H NMR spectroscopy. The 1H NMR signals of trans-stilbene oxide and 2-butanol were enantiomerically separated into two sets of peaks in the presence of CTSP in CDCl3. The competition experiment with acetone suggests that trans-stilbene oxide may be adsorbed on the NH proton of carbamate residues of CTSP. Chemical shift non-equivalence in enantiotopic methyl groups of 2-propanol was observed in the presence of CTSP.
GLOBAL HOLLYWOOD VERSUS NATIONAL PRIDE: The Battle to Film The Forty Days of Musa Dagh
Authors: WELKY DAVID
Published: April 2006

ABSTRACT MGM's attempt to film The Forty Days of Musa Dagh, Franz Werfel's 1933 best-selling novel about the Turkish genocide of Armenians during World War I, nearly touched off a major international incident and alerted Hollywood to the dangers of dealing with foreign subjects in the ideologically charged era of the Great Depression.
When Principle and Authority Collide: Baha'i Responses to the Exclusion of Women from the Universal House of Justice
Authors: Bacquet Karen
Published: April 2006

The Baha'i faith regards the equality of men and women as one of its fundamental tenets, yet excludes women from service on its international governing body, the Universal House of Justice, based on what are believed to be infallible interpretations of Baha'i scripture. This article outlines how the exclusion developed, and describes challenges from liberal Baha'i scholars, as well as the response to these challenges from the administration and rank and file adherents. It demonstrates that, when confronted with a contradiction between a basic principle upheld by religious teaching and loyalty to authority, the Baha'i administration and the majority of adherents have chosen the latter.
Exposure to exogenous estrogens in food: possible impact on human development and health
Authors: Andersson AM , Skakkebaek NE
Published: April 2006

There has been increasing concern about the impact of environmental compounds with hormone-like action on human development and reproductive health over the past decades. An alternative but neglected source of hormone action that may be considered in this connection is hormone residues in meat from husbandry animals treated with sex steroid hormones for growth promotion. Treatment of cattle with naturally occurring or synthetic sex hormones may enhance lean muscle growth and improve feed efficiency and is therefore a very cost effective procedure for cattle producers who have used it for decades in some Western countries, including the USA and Canada. The Joint Food and Agricultural Organisation/World Health Organisation (FAO/WHO) expert committee on food additives (JECFA) and the US Food and Drug Administration (FDA) considered, in 1988, that the residues found in meat from treated animals were safe for the consumers. We have re-evaluated the JECFA conclusions regarding the safety of estradiol residues in meat in the light of recent scientific data, with special emphasis on estradiol levels in prepubertal children. These levels are needed for estimates of the normal daily production rates of estradiol in children, who may be particularly sensitive to low levels of estradiol. In our opinion, the conclusions by JECFA concerning the safety of hormone residues in meat seem to be based on uncertain assumptions and inadequate scientific data. Our concerns can be summarized as follows. 1) The data on residue levels in meat were based on studies performed in the 1970's and 1980's using radioimmunoassay (RIA) methods available at the time. The sensitivity of the methods was generally inadequate to measure precisely the low levels found in animal tissues, and considerable variation between different RIA methods for measuring steroids exists. Therefore the reported residue levels may be subject to considerable uncertainty. 2) Only limited information on the levels of the various metabolites of the steroids was given despite the fact that metabolites also may have biological activity. 3) Reliable data on daily production rates of steroid hormones were and are still lacking in healthy prepubertal children. This lack is crucial as previous guidelines regarding acceptable levels of steroid residues in edible animal tissues have been based on very questionable estimates of production rates in children. Thus, even today the US FDA bases its guidelines on the presumably highly overestimated production rates in prepubertal children given in the JECFA 1988 report. 4) The possible biological significance of very low levels of estradiol is neglected. In conclusion, based on our current knowledge possible adverse effects on human health by consumption of meat from hormone-treated animals cannot be excluded.
Local versus WHO/International Council for Control of Iodine Deficiency Disorders-recommended thyroid volume reference in the assessment of iodine deficiency disorders
Authors: Foo LC , Zulfiqar A , Nafikudin M , Fadzil MT , Asmah AS
Published: April 2006

OBJECTIVE: Iodine deficiency endemia is defined by the goitre prevalence and the median urinary iodine concentration in a population. Lack of local thyroid volume reference data may bring many health workers to use the European-based WHO/International Council for Control of Iodine Deficiency Disorders (ICCIDD)-recommended reference for the assessment of goitre prevalence in children in different developing countries. The present study was conducted in non-iodine-deficient areas in Malaysia to obtain local children's normative thyroid volume reference data, and to compare their usefulness with those of the WHO/ICCIDD-recommended reference for the assessment of iodine-deficiency disorders (IDD) in Malaysia. DESIGN AND METHODS: Cross-sectional thyroid ultrasonographic data of 7410 school children (4004 boys, 3406 girls), aged 7-10 years, from non-iodine-deficient areas (urban and rural) in Peninsular Malaysia were collected. Age/sex- and body surface area/sex-specific upper limits (97th percentile) of normal thyroid volume were derived. Thyroid ultrasonographic data of similar-age children from schools located in a mildly iodine-deficient area, a severely iodine-deficient area, and a non-iodine-deficient area were also collected; spot urines were obtained from these children for iodine determination. RESULTS: The goitre prevalences obtained using the local reference were consistent with the median urinary iodine concentrations in indicating the severity of IDD in the areas studied. In contrast, the results obtained using the WHO/ICCIDD-recommended reference showed lack of congruency with the median urinary iodine concentrations, and grossly underestimated the problem. The local sex-specific reference values at different ages and body surface areas are not a constant proportion of the WHO/ICCIDD-recommended reference. A further limitation of the WHO/ICCIDD-recommended reference is the lack of normative values for children with small body surface areas (<0.8m2) commonly found in the developing countries. CONCLUSION: The observations favour the use of a local reference in the screening of children for thyroid enlargement.
Thyroid volumes in US and Bangladeshi schoolchildren: comparison with European schoolchildren
Authors: Xu F , Sullivan K , Houston R , Zhao J , May W , Maberly G
Published: April 2006

OBJECTIVE: The World Health Organization (WHO) recently adopted thyroid volume ultrasonography results from European schoolchildren as the international reference for assessing iodine deficiency disorders. Our objective was to describe thyroid volumes measured by ultrasonography in US and Bangladeshi schoolchildren and compare these with European schoolchildren. METHODS: Cross-sectional studies were performed in schoolchildren in the US (n=302) and Bangladesh (n=398). Data were collected on the following: thyroid size by palpation and ultrasonography; urinary iodine; age; sex; weight; and height. RESULTS: Applying the new WHO thyroid volume references to the Bangladeshi children resulted in prevalence estimates of enlarged thyroid of 26% based on body surface area (BSA) and 7% based on age. In contrast, in the US children, the prevalence estimates were less than 1% for each reference. In the US children, the best single predictor of thyroid volume was BSA (R2=0.32), followed by weight (R2=0.31). Using linear regression, upper normal limits (97th percentile) of thyroid volume from US children were calculated for BSA, weight and age, and were found to be lower than the corresponding references based on BSA and age from European schoolchildren. CONCLUSIONS: In areas with malnutrition, such as Bangladesh, the BSA reference should be preferred to the reference based on age. Results from the US children indicated that a thyroid volume reference based on weight alone would perform as well as the one based on BSA. European schoolchildren had larger thyroids than US children, perhaps due to a residual effect of iodine deficiency in the recent past in some areas in Europe.
Clinical and morphological features of undifferentiated monomorphous GH/TSH-secreting pituitary adenoma
Authors: Skoric T , Korsic M , Zarkovic K , Plavsic V , Besenski N , Breskovac L , Giljevic Z , Paladino J
Published: April 2006

A 41-year-old male presented with progressive visual defects, acromegaly and hyperthyroidism. After clinical evaluation a giant GH/TSH-secreting pituitary adenoma was diagnosed. Administration of the somatostatin analog octreotide at doses of 150 microg s.c. per day inhibited the secretion of both GH and TSH. A three-week treatment with octreotide prior to surgery led to slight visual improvement and CT scan showed some new necrotic areas within the tumor mass. Transcranial surgery was performed. By immunohistochemical analyses of the adenoma tissue GH, prolactin and beta-chorionic gonadotropin were detected; TSH was negative. Electron microscopy revealed an undifferentiated, monomorphous adenoma with morphological features of an acidophil stem cell adenoma such as the presence of misplaced exocytoses, fibrous bodies and mitochondrial gigantism. However, the tumor cells contained small secretory granules (up to 250 nm) accumulated along the cell membrane characteristic of thyrotrope cells. Furthermore, some adenoma cells were fusiform with long cytoplasmic processes resembling thyrotropes. Two months after the operation CT scan revealed a large residual tumor. Serum GH and TSH levels had increased again and the TSH level was even higher than before the treatment. The patient died suddenly, most probably of lethal arrhythmia. Specimens of the adenoma tissue obtained at autopsy confirmed the previous findings with the exception of positive immunostaining for TSH which was found in less than 1% of the adenoma cells. This undifferentiated, monomorphous GH/TSH-secreting pituitary adenoma represents an entity that is unusual both in its ultrastructural features and clinical manifestations suggesting a cytogenesis from an early, undifferentiated stem cell.
Urinary gonadotropin peptide as acute phase reactant: transient elevation after operation for digestive diseases
Authors: Motoo Y , Watanabe H , Okai T , Sawabu N
Published: April 2006

OBJECTIVE: In order to characterize urinary gonadotropin peptide (UGP) as an acute phase reactant, we focused on the UGP levels after surgical operation. DESIGN: Fifty cases of gastrointestinal cancer, 4 cases of cancers of other organs and 13 cases of benign digestive diseases were enrolled into this study. METHODS: UGP levels were measured using an enzyme immunoassay before and after surgery. RESULTS: Fifty-four (80.6%) of the 67 cases studied showed transient elevations of UGP. Both urinary interleukin (IL)-6 and LH levels were also increased transiently in 49 cases (73.1%). All of these three factors were increased in 38 cases (56.7%), and in 32 (84.2%) of these 38 cases, the order of peak appearance was as follows: IL-6, LH, and UGP. The UGP levels in the group of total gastrectomy were significantly higher than those in the group of partial gastrectomy. CONCLUSIONS: These results suggest that UGP shows a transient peak after surgery, correlating with levels of cytokines such as IL-6. UGP may be an acute phase reactant, and its levels are correlated with the grade of surgical stress.
Somatic MEN1 gene mutation does not contribute significantly to sporadic pituitary tumorigenesis
Authors: Poncin J , Stevenaert A , Beckers A
Published: April 2006

Pituitary adenomas are a common manifestation of multiple endocrine neoplasia type 1 (MEN1) but most of them occur sporadically. There are only a few well defined genetic abnormalities known to occur in these sporadic tumours. The MEN1 gene located on 11q13 has recently been cloned and allelic deletion and mutation analysis studies have implicated the MEN1 gene in a significant fraction of the sporadic counterparts of typical MEN1 neoplasms (parathyroid tumours, insulinomas and gastrinomas). To determine if MEN1 gene inactivation is also involved in the development of sporadic pituitary adenomas, allelic deletions of chromosome 11q13 and MEN1 gene mutations and polymorphisms were assessed in 35 sporadic tumours of the anterior pituitary (9 prolactin-secreting, 8 GH-secreting, 3 TSH-secreting, 2 TSH/GH-secreting, 4 Cushing, 9 silent). Thirty-one tumours were found to be heterozygous for at least one MEN1 intragenic polymorphism (25 cases) or for a flanking gene polymorphism (6 cases). The remaining tumours were not informative. No mutations were found in any tumour except in one prolactinoma which was homozygous or hemizygous for a mutation (1-117 C-->T) in a region close to the promoter. Unfortunately, blood or normal tissue was not available in this case. Our data show that somatic MEN1 mutations do not contribute significantly to tumorigenesis of sporadic pituitary adenomas and suggest that mutation of other genes are likely to contribute to the pathogenesis of these tumours.
Regulation of thymosin beta10 expression by TSH and other mitogenic signals in the thyroid gland and in cultured thyrocytes
Authors: Viglietto G , Califano D , Bruni P , Baldassarre G , Vento MT , Belletti B , Fedele M , Santelli G , Boccia A , Manzo G , Santoro M , Fusco A
Published: April 2006

OBJECTIVE: To investigate the expression of thymosin beta10 - a small conserved acidic protein involved in the inhibition of actin polymerization - in human and experimental thyroid goiters as well as the regulation exerted by TSH on thymosin beta10 expression in thyroid follicular cells both in vivo and in vitro. DESIGN: To this aim, we have used 5 bioptic specimens from patients affected by thyroid goiter, a well known experimental model of thyroid goitrogenesis (rat fed with the drug propylthiouracil) and a cultured rat thyroid cell line (PC Cl 3 cells) as a model system. RESULTS: We report that the mRNA expression of thymosin beta10 is markedly enhanced in human goiters compared with normal thyroid. In vivo results showed that the steady-state level of thymosin beta10 mRNA is up-regulated in the thyroid gland of propylthiouracil-fed rats in parallel with follicular cell proliferation: iodide administration to goitrous rats, which induced a marked involution of thyroid hyperplasia, reduced the mRNA level of thymosin beta10. Finally, in vitro studies showed that in cultured rat thyrocytes, the expression of thymosin beta10 mRNA is induced in a time- and dose-dependent manner by the activation of pathways which are mitogenic for thyroid cells (i.e. the protein kinase (PK) A and PKC pathways). CONCLUSION: Taken together, the findings reported here demonstrate that thymosin beta10 expression is regulated by extracellular signals that stimulate growth of thyroid cells both in vitro and in vivo, and suggest a role for this protein in thyroid diseases characterized by proliferation of follicular cells.
Calcium/calmodulin kinase IV pathway is involved in the transcriptional regulation of the corticotropin-releasing hormone gene promoter in neuronal cells
Authors: Yamamori E , Asai M , Yoshida M , Takano K , Itoi K , Oiso Y , Iwasaki Y
Published: April 2006

Although corticotropin-releasing hormone (CRH) plays a pivotal role in the regulation of the hypothalamo-pituitary-adrenal axis, the mechanism of CRH gene expression in the neuronal cell is not completely understood. In this study, we examined the transcriptional regulation of human CRH gene 5′-promoter, using a human BE(2)C neuroblastoma cell line expressing intrinsic CRH. In particular, we focused on the involvement of calmodulin kinases (CaMKs), which are known to play an important role in excitation-induced gene expression through the rise in intracellular calcium in the central nervous system. RT-PCR analysis confirmed the expression of CaMK as well as CRH mRNA in BE(2)C cells. When we introduced ≈1.1 kb of the 5′-promoter region of the human CRH fused with luciferase reporter gene into the cells, a substantial transcriptional activity was observed, and this was further increased by the activation of the cAMP/PKA pathway. We then examined the effect of activation of CaMKs by introducing the expression vectors of each kinase, revealing a potent stimulatory effect of CaMKIV, but no effect of CaMKII. Depolarization of the cells caused an increase in CRH promoter activity, which was completely abolished by the treatment with the CaMK antagonist K252a. Interestingly, KCREB, a dominant negative form of CREB, antagonized the effect of the CaMKIV-mediated effect. Altogether, we conclude that not only the cAMP/PKA but also the calcium/CaMKIV signaling pathway is involved in the regulation of CRH gene expression. Furthermore, CREB is thought to be involved in CaMK- as well as cAMP/PKA-mediated CRH gene expression. Since the CRH gene is expressed in the neuronal cells of the hypothalamus, the calcium/CaMKIV signaling pathway may play an important role in the excitation-mediated regulation of CRH synthesis.
Comparative uterine gene expression analysis after dioxin and estradiol administration
Authors: Watanabe H , Suzuki A , Goto M , Ohsako S , Tohyama C , Handa H , Iguchi T
Published: April 2006

The environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) adversely affects many organisms. TCDD exposure is known to be associated with abnormal development, hepatotoxicity and endocrine effects. It has also been reported to have antiestrogenic activity in addition to estrogenic activity. In order to clarify the effects of TCDD in the uterus, we evaluated the patterns of gene expression after TCDD and estradiol administration. Of the 10 000 arrayed genes, only a few were affected by both estradiol and TCDD. Although the subset of genes that responded to estrogen was also activated by TCDD, the response to TCDD was more limited than that observed in response to estradiol. Therefore, according to our analysis of gene expression patterns, TCDD had partial and weak estrogenic activity in the uterus.
The early gene Broad is involved in the ecdysteroid hierarchy governing vitellogenesis of the mosquito Aedes aegypti
Authors: Chen L , Zhu J , Sun G , Raikhel A S
Published: April 2006

The broad (br ) gene, encoding a family of C2H2 type zinc-finger DNA-binding proteins, has been shown to act as a crucial member of the 20-hydroxyecdysone (20E) regulatory hierarchy in the fruitfly, Drosophila melanogaster and the moth, Manduca sexta. In this study, we have shown that the br gene is involved in the 20E-regulatory hierarchy controlling vitellogenesis in the mosquito, Aedes aegypti. Unlike E74 and E75 early genes, expression of br was activated in previtellogenic females, during a juvenile hormone (JH)-dependent period. The levels of Z1, Z2 and Z4 isoform mRNA were elevated in the fat body of 2-day-old females after in vitro exposure to JH III. However, JH III repressed 20E activation of br in 3-to 5-day-old females, indicating a switch in hormonal commitment. Expression of Z1, Z2 and Z4 was stimulated after blood feeding in both vitellogenic tissues, the fat body and the ovary, corresponding to peaks of ecdysteroid titers. In the fat body, the mRNA profiles of these three isoforms correlated well with those of yolk protein precursor (YPP) genes. These BR isoforms were activated by 20E in fat bodies cultured in vitro and behaved as early genes, with a self-repressive autoregulatory loop that can be blocked by the protein inhibitor, cyclohexamide. Multiple binding sites for all four BR isoforms were present in the 5′-regulatory region of the major YPP gene, vitellogenin (Vg). Effects of BR isoforms on the expression of Vg have been demonstrated by cell transfection analysis. In particular, BR isoforms by themselves had no effects on the Vg promoter. However, Z1 and Z4 each repressed Aedes aegypti ecdysone receptor (EcR)/Ultraspiracle (USP)-mediated 20E activation of the Vg promoter, while Z2 enhanced activation of the Vg promoter by AaEcR/AaUSP in the presence of 20E. Z3 had no obvious effect in the same experiment. These results suggested that BR isoforms are essential for proper activation and termination of the Vg gene in response to 20E. Overall, our study implicated br in the regulation of mosquito vitellogenesis.
Transcriptional regulation of glucose-6-phosphatase catalytic subunit promoter by insulin and glucose in the carnivorous fish, Sparus aurata
Authors: Salgado M C , Metón I , Egea M , Baanante I V
Published: April 2006

Increase in glucose-6-phosphatase catalytic subunit (G6Pase, G6pc) transcription enhances hepatic glucose production in non-insulin-dependent diabetes mellitus (NIDDM). The fact that carnivorous fish is an alternative model to study NIDDM led us to clone and characterise the first G6pc promoter region reported for fish and non-mammalian animals. The 5′-flanking region of G6pc from gilthead sea bream (Sparus aurata) was isolated by chromosome walking. With SMART RACE-PCR, the transcription start site was located 106 base pairs (bp) upstream of the translational start. Transfection analysis in HepG2 cells located a functional promoter in the 850 bp 5′-flanking isolated fragment (positions −770 to +80 relative to the transcription start). Sequential 5′-deletion analysis of the promoter fragment revealed that a core functional promoter for basal transcription is comprised within the 190 bp upstream of the transcription start site. In vivo, glucose and insulin reduced G6Pase mRNA levels in the fish liver. Transfection experiments in HepG2 cells showed that insulin repressed S. aurata G6pc under high-glucose conditions. Synergistic activation of piscine G6pc promoter was induced by cotransfection with expression plasmids for hepatocyte nuclear factor-4α (HNF-4α) and peroxisome proliferator-activated receptor-γ coactivator-1 (PGC-1α). No direct relationship was found between PGC-1α coactivation of HNF-4α transactivation and the repressive effect of insulin. Interestingly, insulin hardly affected G6pc promoter activity in the absence of glucose, suggesting that a reduced capacity of insulin-dependent repression of piscine G6pc may lead to insulin resistance in carnivorous fish.
The orphan receptor Rev-erbα gene is a target of the circadian clock pacemaker
Authors: Triqueneaux Gérard , Thenot Sandrine , Kakizawa Tomoko , Antoch Marina P , Safi Rachid , Takahashi Joseph S , Delaunay Franck , Laudet Vincent
Published: April 2006

Rev-erbα is a ubiquitously expressed orphan nuclear receptor which functions as a constitutive transcriptional repressor and is expressed in vertebrates according to a robust circadian rhythm. We report here that two Rev-erbα mRNA isoforms, namely Rev-erbα1 and Rev-erbα 2, are generated through alternative promoter usage and that both show a circadian expression pattern in an in vitro system using serum-shocked fibroblasts. Both promoter regions P1 (Rev-erbα1) and P2 (Rev-erbα2) contain several E-box DNA sequences which function as response elements for the core circadian-clock components: CLOCK and BMAL1. The CLOCK–BMAL1 heterodimer stimulates the activity of both P1 and P2 promoters in transient transfection assay by 3–6-fold. This activation was inhibited by the overexpression of CRY1, a component of the negative limb of the circadian transcriptional loop. Critical E-box elements were mapped within both promoters. This regulation is conserved in vertebrates since we found that the CLOCK–BMAL1 heterodimer also regulates the zebrafish Rev-erbα gene. In line with these data Rev-erbα circadian expression was strongly impaired in the livers of Clock mutant mice and in the pineal glands of zebrafish embryos treated with Clock and Bmal1 antisense oligonucleotides. Together these data demonstrate that CLOCK is a critical regulator of Rev-erbα circadian gene expression in evolutionarily distant vertebrates and suggest a role for Rev-erbα in the circadian clock output.
RNA interference and the use of small interfering RNA to study gene function in mammalian systems
Authors: Bantounas I , Phylactou L A , Uney J B
Published: April 2006

In the past 2 years, extraordinary developments in RNA interference (RNAi)-based methodologies have seen small interfering RNAs (siRNA) become the method of choice for researchers wishing to target specific genes for silencing. In this review, an historic overview of the biochemistry of the RNAi pathway is described together with the latest advances in the RNAi field. Particular emphasis is given to strategies by which siRNAs are used to study mammalian gene function. In this regard, the use of plasmid-based and viral vector-based systems to mediate long-term RNAi in vitro and in vivo are described. However, recent work has shown that non-specific silencing effects and activation of the interferon response may occur following the use of some siRNA and delivery vector combinations. Future goals must therefore be to understand the mechanisms by which siRNA delivery leads to unwanted gene silencing effects in cells and, in this way, RNAi technology can reach its tremendous potential as a scientific tool and ultimately be used for therapeutic purposes.
Regulation of gonadotropin subunit gene transcription
Authors: Burger L L , Haisenleder D J , Dalkin A C , Marshall J C
Published: April 2006

Reproductive function in mammals is regulated by the pituitary gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH). LH and FSH are secreted by the gonadotrope cell and act on the gonad in a sequential and synergistic manner to initiate sexual maturation and maintain cyclic reproductive function. The synthesis and secretion of LH and FSH are regulated mainly by the pulsatile release of the hypothalamic decapeptide hormone gonadotropin-releasing hormone (GnRH). The control of differential LH and FSH synthesis and secretion is complex and involves the interplay between the gonads, hypothalamus and pituitary. In this review, the transcriptional regulation of the gonadotropin subunit genes is discussed in a physiologic setting, and we aimed to examine the mechanisms that drive those changes.
Peripherally administered [Nle4,d-Phe7]-α-melanocyte stimulating hormone increases resting metabolic rate, while peripheral agouti-related protein has no effect, in wild type C57BL/6 and ob/ob mice
Authors: Hoggard N , Rayner D V , Johnston S L , Speakman J R
Published: April 2006

The melanocortin system coordinates the maintenance of energy balance via the regulation of both food intake and energy expenditure. Leptin, a key adipogenic hormone involved in the regulation of energy balance is thought to act by stimulating production, in the hypothalamic arcuate nucleus, of α-melanocyte stimulating hormone (αMSH), a potent agonist of MC3/4 melanocortin receptors located in the paraventricular nucleus of the hypothalamus. Additionally leptin inhibits release of agouti-related protein (AgRP), an MC4R antagonist. During periods of caloric restriction, weight loss is not sustained because compensatory mechanisms, such as reduced resting metabolic rate (RMR) are brought into play. Understanding how these compensatory systems operate may provide valuable targets for pharmaceutical therapies to support traditional dieting approaches. As circulating leptin is reduced during caloric restriction, it may mediate some of the observed compensatory responses.

In addition to decreases in circulating leptin levels, circulating AgRP is increased during fasting in rodents while αMSH is decreased. As central administration of AgRP depresses metabolism, we hypothesised that the peripheral rise in AgRP might be involved in signalling the depression of RMR during food restriction. We hypothesised that changes in plasma AgRP and αMSH may coordinate the regulation of changes in energy expenditure acting through central MC4 melanocortin receptors via the sympathetic nervous system.

We show here that acute peripherally administered AgRP at supra-physiological concentrations in both lean (C57BL/6) and obese leptin-deficient (ob/ob) mice does not depress RMR, possibly because it crosses the blood–brain barrier very slowly compared with other metabolites. However, in vitro AgRP can decrease leptin secretion, by approximately 40%, from adipocytes into culture medium and may via this axis have an effect on energy metabolism during prolonged caloric restriction. In contrast, peripheral [Nle4,d-Phe7]-α MSH produced a large and sustained increase in resting energy expenditure (0.15 ml O2/min; P <0.05) with a similar response in leptin-deficient ob/ob mice (0.27 ml O2/min) indicating that this effect is independent of the status of leptin production in the periphery. In both cases respiratory exchange ratio and the levels of energy expended on spontaneous physical activity were unaffected by the administration of peripheral [Nle4,d-Phe7]-α MSH. In conclusion, αMSH analogues that cross the blood–brain barrier may significantly augment dietary restriction strategies by sustaining elevated RMR.
Geodynamic setting of the Birimian volcanism in central Ivory Coast (western Africa) and its place in the Palaeoproterozoic evolution of the Man Shield
Authors: Pouclet André , Doumbia Siaka , Vidal Max
Published: April 2006

Palaeoproterozoic volcanic formations having different geochemical features are described in the Katiola-Marabadiassa area (Central Ivory Coast). They consist of (i) metamorphic mafic rocks belonging to the greenstone belts, (ii) rhyodacites intruded into the greenstone belts and interpreted as sub-volcanic apophyses of TTG plutons, and (iii) calc-alkaline andesitic lava interbedded in the lower sedimentary pile of the Bandama Basin. The greenstone belt rocks have a magmatic signature of ocean floor tholeiites. They were generated from moderate partial melting of a fairly depleted spinel lherzolite source. The rhyodacites show the same compositions as the TTG granitoids of the belt. These TTGs generated from melting of garnet-bearing amphibolite, derived from subducted oceanic crust, but also from peridotite melting of the fertilized mantle wedge. The andesites show a common composition of active continental margin potassic calc-alkaline lavas. However, they do not constitute a volcanic belt, but belong to an intracontinental basin settled in a wrench tectonic system. They probably generated from remelting of sub-crustal metasomatised mantle.

The tectono-magmatism story of the Katiola-Marabadiassa area comprises four stages. A similar evolution is found in other belt-and-basin areas in Ivory Coast. A review of lithostratigraphic and chronological data of the Birimian terrains leads us to compare the four-stage model of the Central Ivory Coast to the West-African Palaeoproterozoic evolution. The first stage corresponds to ocean crust formation, by mid-ocean ridge accretion and volcanic arc building. The second stage, partly overlapping the previous one, is convergent and lasted from oceanic crust stacking to TTG and associated greenstone belt formation. It led to a protocontinental crust accretion by docking of granitized blocks, from ca 2200 Ma to 2110 Ma. The third stage corresponds to the formation of intracontinental basins by reorganization of the granitoid-greenstone shields and of the remnant oceanic basins, between 2118 Ma and 2093 Ma. It was associated with calc-alkaline magma production. The fourth stage is characterized by transtensional stress, with the closure of the basins by left-lateral wrenching along N-S faults, and by emplacement of new potassic granitoids until 2072 Ma.
The Bay of Mont-Saint-Michel northeastern littoral: an illustrative case of coastal sedimentary body evolution and stratigraphic organization in a transgressive/highstand context
Authors: Tessier Bernadette , Billeaud Isabelle , Lesueur Patrick
Published: April 2006

The aim of the present paper is primarily of pedagogic order. It presents the landscapes of the northeastern littoral of the Bay of Mont-Saint-Michel and explains how these landscapes can be understood in terms of stratigraphic organization and evolution. The northeastern coast of the Bay displays contrasted landscapes and morphodynamic processes along a restricted area. This coast consists in an elongated sandy barrier made of beaches and aeolian dunes, and back barrier tidal flats. A wide estuarine channel-and shoal system migrates in front of the beaches. Because of direct wave attack, the barrier experiences a severe retreat in the north whereas in the south, due to sufficient sediment supply, beaches and dunes tend to prograde. These contrasted processes give rise to different sedimentary bodies and surfaces, the nature, geometry, extension, and time-scale of which are described and discussed through examination of the landscapes. The present-day depositional system can be thus used to illustrate and test sequence stratigraphic concepts such as system tracts, ravinement surfaces and process time-scales.