bluuebunny/crossref_metadata_2025 huggingface dataset:
Inducible cAMP early repressor suppresses gastrin-mediated activation of cyclin D1 and c-fosgene expression
Authors: Steigedal Tonje S. , Bruland Torunn , Misund Kristine , Thommesen Liv , Lægreid Astrid
Published: December 2006

The gastric hormone gastrin and its precursors promote proliferation in several gastrointestinal cell types. Here we show that gastrin induces transcription of cell cycle gene cyclin D1 and protooncogene c- fos in the neuroendocrine pancreatic cell line AR42J and that this gastrin response is inhibited by endogenous inducible cAMP early repressor (ICER). The transcriptional repressor ICER is known to downregulate both its own expression and the expression of other genes containing cAMP-responsive elements (CREs). Using siRNA, we also show that CRE promoter elements are the targets of endogenous ICER in AR42J cells as well as in the neuroendocrine cell line RIN5F. Our results suggest that ICER plays an important role in molecular mechanisms governing gastrin-mediated growth by modulating gastrin's transcriptional activation of growth-related genes. Our finding that ICER modulates pituitary adenylate cyclase-activating polypeptide-activated gene expression also indicates a regulatory effect of ICER in the responses of neuroendocrine cells to peptides other than gastrin.
Ryanodine receptor dysfunction and triggered activity in the heart
Authors: Katra Rodolphe P. , Oya Toshiyuki , Hoeker Gregory S. , Laurita Kenneth R.
Published: December 2006

Arrhythmogenesis has been increasingly linked to cardiac ryanodine receptor (RyR) dysfunction. However, the mechanistic relationship between abnormal RyR function and arrhythmogenesis in the heart is not clear. We hypothesize that, under abnormal RyR conditions, triggered activity will be caused by spontaneous calcium release (SCR) events that depend on transmural heterogeneities of calcium handling. We performed high-resolution optical mapping of intracellular calcium and transmembrane potential in the canine left ventricular wedge preparation ( n = 28). Rapid pacing was used to initiate triggered activity under normal and abnormal RyR conditions induced by FKBP12.6 dissociation and β-adrenergic stimulation (20–150 μM rapamycin, 0.2 μM isoproterenol). Under abnormal RyR conditions, almost all preparations experienced SCRs and triggered activity, in contrast to control, rapamycin, or isoproterenol conditions alone. Furthermore, under abnormal RyR conditions, complex arrhythmias (monomorphic and polymorphic tachycardia) were commonly observed. After washout of rapamycin and isoproterenol, no triggered activity was observed. Surprisingly, triggered activity and SCRs occurred preferentially near the epicardium but not the endocardium ( P < 0.01). Interestingly, the occurrence of triggered activity and SCR events could not be explained by cytoplasmic calcium levels, but rather by fast calcium reuptake kinetics. These data suggest that, under abnormal RyR conditions, triggered activity is caused by multiple SCR events that depend on the faster calcium reuptake kinetics near the epicardium. Furthermore, multiple regions of SCR may be a mechanism for multifocal arrhythmias associated with RyR dysfunction.
Maspin: The New Frontier
Authors: Khalkhali-Ellis Zhila
Published: December 2006

Maspin (mammary serine protease inhibitor) was identified in 1994 by subtractive hybridization analysis of normal mammary tissue and breast cancer cell lines. Subsequently, emerging evidence portrays maspin as a multifaceted protein, interacting with diverse group of intercellular and extracellular proteins, regulating cell adhesion, motility, apoptosis, and angiogenesis and critically involved in mammary gland development. The tissue-specific expression of maspin is epigenetically controlled, and aberrant methylation of maspin promoter is closely associated with maspin gene silencing. Identification of new tissue sites expressing maspin and novel maspin-binding partners has expanded the horizon for maspin research and promises maspin-based therapeutic approaches for combating cancer. This perspective briefly outlines the past and present strides in deciphering this unique molecule and speculates on new frontiers in maspin research and prospects of maspin as a diagnostic/prognostic indicator in cancer.
Peptide Aptamers with Binding Specificity for the Intracellular Domain of the ErbB2 Receptor Interfere with AKT Signaling and Sensitize Breast Cancer Cells to Taxol
Authors: Kunz Christian , Borghouts Corina , Buerger Claudia , Groner Bernd
Published: December 2006

The ErbB2 receptor tyrosine kinase is overexpressed in ∼30% of breast tumor cases and its overexpression correlates with an unfavorable prognosis. A major contributor for this course of the disease is the insensitivity of these tumors toward chemotherapy. Monoclonal antibodies, inhibiting the ligand-induced activation of the receptor and tyrosine kinase inhibitors acting on the intrinsic enzymatic activity of the intracellular domain, have been developed as targeted drugs. Both have been shown to be beneficial for breast cancer patients. We targeted a third aspect of receptor function: its association with intracellular signaling components. For this purpose, we selected peptide aptamers, which specifically interact with defined domains of the intracellular part of the receptor. The peptide aptamers were selected from a random peptide library using a yeast two-hybrid system with the intracellular tyrosine kinase domain of ErbB2 as a bait construct. The peptide aptamer AII-7 interacts with high specificity with the ErbB2 receptor in vitro and in vivo. The aptamers colocalized with the intracellular domain of ErbB2 within cells. We investigated the functional consequences of the aptamer interaction with the ErbB2 receptor within tumor cells. The aptamer sequences were either expressed intracellularly or introduced into the cells as recombinant aptamer proteins. The phosphorylation of p42/44 mitogen-activated protein kinase was nearly unaffected and the activation of signal transducers and activators of transcription-3 was only modestly reduced. In contrast, they strongly inhibited the induction of AKT kinase in MCF7 breast cancer cells treated with heregulin, whereas AKT activation downstream of insulin-like growth factor I or epidermal growth factor receptor was not or only slightly affected. High AKT activity is responsible for the enhanced resistance of ErbB2-overexpressing cancer cells toward chemotherapeutic agents. Peptide aptamer interference with AKT activation resulted in the restoration of regular sensitivity of breast cancer cells toward Taxol. (Mol Cancer Res 2006;4(12):983–98)
Use of an Aggressive MCF-7 Cell Line Variant, TMX2-28, to Study Cell Invasion in Breast Cancer
Authors: Gozgit Joseph M. , Pentecost Brian T. , Marconi Sharon A. , Otis Christopher N. , Wu Chuanyue , Arcaro Kathleen F.
Published: December 2006

An estrogen receptor–negative variant of the MCF-7 breast cancer cell line, TMX2-28, was used as a model in which to study breast cancer cell invasion. Using a reconstituted basement membrane (Matrigel) assay to evaluate cell invasion, we determined that TMX2-28 cells are more invasive than MCF-7 cells and that the invasiveness of TMX2-28 is similar to that of the aggressive MDA-MB-231 breast cancer cell line. TMX2-28 cells displayed a rounded, epithelial cell–like morphology, suggesting an amoeboid mode of cell invasion, in contrast to the mesenchymal mode of invasion characteristic of spindle-shaped, fibroblast-like MDA-MB-231 cells. Using real-time reverse transcription-PCR, we found that mitogen-inducible gene 2 (MIG2) is expressed at a 17-fold higher level in TMX2-28 cells than in nonaggressive MCF-7 cells and that MIG2 mRNA levels are low in the nontumorigenic human mammary epithelial cell line, 184. We determined that MIG2 plays a role in cell invasion by using small interfering RNA (siRNA) to suppress the expression of MIG2 mRNA levels in TMX2-28 cells. TMX2-28 cell invasion was reduced by 48% when the cells were transfected with siRNAs targeting MIG2, relative to cells transfected with siRNAs against glyceraldehyde-3-phosphate dehydrogenase. Finally, MIG2 expression was evaluated in reductive mammoplasty and breast tumor tissue. Although all 21 normal tissues from reduction mammoplasty showed immunoreactivity for MIG2, ranging from weak (62%) to strong (24%), only half of the 34 formalin-fixed breast tumors showed immunoreactivity for MIG2. Of these 17 positive cases, 10 were considered to overexpress MIG2 (moderate to strong staining). Examination of 30 frozen breast tumors supported the finding that MIG2 is overexpressed in a subset of breast cancers. We suggest that MIG2's normal regulation and function are disrupted in breast cancer. (Mol Cancer Res 2006;4(12):905–13)
Ubiquitin Hubs in Oncogenic Networks
Authors: Crosetto Nicola , Bienko Marzena , Dikic Ivan
Published: December 2006

Ubiquitin is an important regulator of diverse biological functions including cell cycle progression, apoptosis, cell proliferation, and DNA damage responses. Crucial proteins involved in the control of such diverse functions are modified by ubiquitin and are frequently altered during oncogenesis. Here, we define such proteins as key-nodes regulated by ubiquitin, discuss examples of their oncogenic aberrations, and indicate how pharmacologic manipulation of such molecular hubs might improve anticancer therapy. (Mol Cancer Res 2006;4(12):899–904)
Global Gene Expression Profiling of Bacillus subtilis in Response to Ammonium and Tryptophan Starvation as Revealed by Transcriptome and Proteome Analysis
Authors: Tam Le Thi , Eymann Christine , Antelmann Haike , Albrecht Dirk , Hecker Michael
Published: December 2006

The global gene expression profile of Bacillus subtilis in response to ammonium and tryptophan starvation was analyzed using transcriptomics and proteomics which gained novel insights into these starvation responses. The results demonstrate that both starvation conditions induce specific, overlapping and general starvation responses. The TnrA regulon, the glutamine synthetase (glnA) as well as the σL-dependent bkd and roc operons were most strongly and specifically induced after ammonium starvation. These are involved in the uptake and utilization of ammonium and alternative nitrogen sources such as amino acids, γ-aminobutyrate, nitrate/nitrite, uric acid/urea and oligopeptides. In addition, several carbon catabolite-controlled genes (e.g. acsA, citB), the α-acetolactate synthase/-decarboxylase alsSD operon and several aminotransferase genes were specifically induced after ammonium starvation. The induction of σF- and σE-dependent sporulation proteins at later time points in ammonium-starved cells was accompanied by an increased sporulation frequency. The specific response to tryptophan starvation includes the TRAP-regulated tryptophan biosynthesis genes, some RelA-dependent genes (e.g. adeC, ald) as well as spo0E. Furthermore, we recognized overlapping responses between ammonium and tryptophan starvation (e.g. dat, maeN) as well as the common induction of the CodY and σH general starvation regulons and the RelA-dependent stringent response. Many genes encoding proteins of so far unknown functions could be assigned to specifically or commonly induced genes.
Seroprevalence of Hepatitis B and C Viruses in Patients with Chronic Kidney Disease in the Predialysis Stage at a University Hospital in Turkey
Authors: Sit Dede , Kadiroglu Ali Kemal , Kayabasi Hasan , Yilmaz M. Emin , Goral Vedat
Published: December 2006

Background: Hepatitis B (HBV) and C (HCV) viruses are the most common viruses that cause viral infections among the hemodialysis patients. Objectives: To assess the prevalence of HBV and HCV in predialytic chronic kidney disease (CKD) patients. Design: A cross-sectional study. Subjects: 171 consecutive predialytic CKD patients. Measurements: Third-generation micro-ELISA assay was used for hepatitis B surface antigen (HBsAg), antibody to hepatitis B core (anti-HBc) and surface antibody (anti-HBs), secretory form of hepatitis B envelop antigen (HBeAg), antibody to secretory form of hepatitis B envelop antigen (anti-HBe), and ELISA for antibody to hepatitis C virus (anti-HCV). Results: The main causes of CKD were 29.8% diabetic nephropathy, 19.9% chronic glomerulonephritis, 16.3% hypertensive nephrosclerosis, 14.0% unknown, 5.3% amyloidosis, 4.7% autosomal-dominant polycystic kidney disease, 4.1% chronic tubuluointerstitial nephritis, 3.5% malignancies, 1.7% benign prostatic hypertrophy, 0.6% Alport syndrome. The seroprevalence of hepatitis was: HBsAg 10.5%, anti-HBc 36.8%, anti-HBs 28.7%, HBeAg 5.3%, anti-HBe 32.7%, anti-HCV 7% and HBsAg+anti-HCV 0.6%. Conclusions: The seroprevalence of HBsAg and anti-HCV among predialytic CKD patients was similar to our patients in hemodialysis program.
Student Engagement in the Teaching and Learning of Grammar
Authors: Smagorinsky Peter , Wright Laura , Augustine Sharon Murphy , O’Donnell-Allen Cindy , Konopak Bonnie
Published: December 2006

This article reports a study of coauthor Laura Wright as she learned to teach secondary school grammar in four settings: university teacher education program, student teaching, her first job, and second job. Data for her university program came from Laura’s journals and projects from her course work. Data from student teaching and her first job included interviews and field notes from observations and interviews and self-reports by Laura of teaching conducted on other occasions. Information from her second job came from self-reports by Laura. The data were analyzed using a system that identified the pedagogical tools Laura employed and the attributions she made for learning how to use them. The data suggest that Laura sought to teach in ways that students found engaging, meaningful, enjoyable, and relevant. How she was able to make grammar instruction fit this goal varied according to the setting in which her instruction took place.
CBFB-MYH11 hinders early T-cell development and induces massive cell death in the thymus
Authors: Zhao Ling , Cannons Jennifer L. , Anderson Stacie , Kirby Martha , Xu Liping , Castilla Lucio H. , Schwartzberg Pamela L. , Bosselut Rémy , Liu P. Paul
Published: December 2006

Recent studies suggest that the chromosome 16 inversion, associated with acute myeloid leukemia M4Eo, takes place in hematopoietic stem cells. If this is the case, it is of interest to know the effects of the resulting fusion gene, CBFB-MYH11, on other lineages. Here we studied T-cell development in mice expressing Cbfb-MYH11 and compared them with mice compound-heterozygous for a Cbfb null and a hypomorphic GFP knock-in allele (Cbfb−/GFP), which had severe Cbfb deficiency. We found a differentiation block at the DN1 stage of thymocyte development in Cbfb-MYH11 knock-in chimeras. In a conditional knock-in model in which Cbfb-MYH11 expression was activated by Lck-Cre, there was a 10-fold reduction in thymocyte numbers in adult thymus, resulting mainly from impaired survival of CD4+CD8+ thymocytes. Although Cbfb-MYH11 derepressed CD4 expression efficiently in reporter assays, such derepression was less pronounced in vivo. On the other hand, CD4 expression was derepressed and thymocyte development was blocked at DN1 and DN2 stages in E17.5 Cbfb−/GFP thymus, with a 20-fold reduction of total thymocyte numbers. Our data suggest that Cbfb-MYH11 suppressed Cbfb in several stages of T-cell development and provide a mechanism for CBFB-MYH11 association with myeloid but not lymphoid leukemia.
Organ procurement organizations Internet enrollment for organ donation: Abandoning informed consent
Authors: Woien Sandra , Rady Mohamed Y , Verheijde Joseph L , McGregor Joan
Published: December 2006

Background

Requirements for organ donation after cardiac or imminent death have been introduced to address the transplantable organs shortage in the United States. Organ procurement organizations (OPOs) increasingly use the Internet for organ donation consent.

Methods

An analysis of OPO Web sites available to the public for enrollment and consent for organ donation. The Web sites and consent forms were examined for the minimal information recommended by the United States Department of Health and Human Services for informed consent. Content scores were calculated as percentages of data elements in four information categories: donor knowledge, donor consent reinforcement, donation promotion, and informed consent.

Results

There were 60 Web sites for organ donation enrollment serving the 52 states. The median percent (10 percentile-90 percentile) content scores of the Web sites for donor knowledge, donor consent reinforcement, and donation promotion were 33% (20–47), 79% (57–86), and 75% (50–100), respectively. The informed consent score was 0% (0–33). The content scores for donor knowledge and informed consent were significantly lower than donor consent reinforcement and donation promotion for all Web sites (P < .05). The content scores for the four categories were similar among the 11 regions of the United Network for Organ Sharing.

Conclusion

The Web sites and consent forms for public enrollment in organ donation do not fulfill the necessary requirements for informed consent. The Web sites predominantly provide positive reinforcement and promotional information rather than the transparent disclosure of organ donation process. Independent regulatory oversight is essential to ensure that Internet enrollment for organ donation complies with legal and ethical standards for informed consent.
Regulation of redox metabolism in the mouse oocyte and embryo
Authors: Dumollard Rémi , Ward Zoe , Carroll John , Duchen Michael R.
Published: December 2006

Energy homeostasis of the oocyte is a crucial determinant of fertility. Following ovulation, the oocyte is exposed to the unique environment of the Fallopian tube, and this is reflected in a highly specialised biochemistry. The minute amounts of tissue available have made the physiological analysis of oocyte intermediary metabolism almost impossible. We have therefore used confocal imaging of mitochondrial and cytosolic redox state under a range of conditions to explore the oxidative metabolism of intermediary substrates. It has been known for some time that the early mouse embryo metabolises external pyruvate and lactate but not glucose to produce ATP. We now show at the level of single oocytes, that supplied glucose has no effect on the redox potential of the oocyte. Pyruvate is a cytosolic oxidant but a mitochondrial reductant,while lactate is a strong cytosolic reductant via the activity of lactate dehydrogenase. Unexpectedly, lactate-derived pyruvate appears to be diverted from mitochondrial oxidation. Our approach also reveals that the level of reduced glutathione (GSH) in the oocyte is maintained by glutathione reductase, which oxidises intracellular NADPH to reduce oxidised glutathione. Surprisingly, NADPH does not seem to be supplied by the pentose phosphate pathway in the unfertilised oocyte but rather by cytosolic NADP-dependent isocitrate dehydrogenase. Remarkably, we also found that the oxidant action of pyruvate impairs development, demonstrating the fundamental importance of redox state on early development.
Long-distance RNA–RNA interactions between terminal elements and the same subset of internal elements on the potato virus X genome mediate minus- and plus-strand RNA synthesis
Authors: Hu Bin , Pillai-Nair Neeta , Hemenway Cynthia
Published: December 2006

Potexvirus genomes contain conserved terminal elements that are complementary to multiple internal octanucleotide elements. Both local sequences and structures at the 5′ terminus and long-distance interactions between this region and internal elements are important for accumulation of potato virus X (PVX) plus-strand RNA in vivo. In this study, the role of the conserved hexanucleotide motif within SL3 of the 3′ NTR and internal conserved octanucleotide elements in minus-strand RNA synthesis was analyzed using both a template-dependent, PVX RNA-dependent RNA polymerase (RdRp) extract and a protoplast replication system. Template analyses in vitro indicated that 3′ terminal templates of 850 nucleotides (nt), but not 200 nt, supported efficient, minus-strand RNA synthesis. Mutational analyses of the longer templates indicated that optimal transcription requires the hexanucleotide motif in SL3 within the 3′ NTR and the complementary CP octanucleotide element 747 nt upstream. Additional experiments to disrupt interactions between one or more internal conserved elements and the 3′ hexanucleotide element showed that long-distance interactions were necessary for minus-strand RNA synthesis both in vitro and in vivo. Additionally, multiple internal octanucleotide elements could serve as pairing partners with the hexanucleotide element in vivo. These cis-acting elements and interactions correlate in several ways to those previously observed for plus-strand RNA accumulation in vivo, suggesting that dynamic interactions between elements at both termini and the same subset of internal octanucleotide elements are required for both minus- and plus-strand RNA synthesis and potentially other aspects of PVX replication.
Impact of Adjustment for Quality on Results of Metaanalyses of Diagnostic Accuracy
Authors: Leeflang Mariska , Reitsma Johannes , Scholten Rob , Rutjes Anne , Di Nisio Marcello , Deeks Jon , Bossuyt Patrick
Published: December 2006

Background: We examined whether and to what extent different strategies of defining and incorporating quality of included studies affect the results of metaanalyses of diagnostic accuracy.

Methods: We evaluated the methodological quality of 487 diagnostic-accuracy studies in 30 systematic reviews with the QUADAS (Quality Assessment of Diagnostic-Accuracy Studies) checklist. We applied 3 strategies that varied both in the definition of quality and in the statistical approach to incorporate the quality-assessment results into metaanalyses. We compared magnitudes of diagnostic odds ratios, widths of their confidence intervals, and changes in a hypothetical clinical decision between strategies.

Results: Following 2 definitions of quality, we concluded that only 70 or 72 of 487 studies were of “high quality”. This small number was partly due to poor reporting of quality items. None of the strategies for accounting for differences in quality led systematically to accuracy estimates that were less optimistic than ignoring quality in metaanalyses. Limiting the review to high-quality studies considerably reduced the number of studies in all reviews, with wider confidence intervals as a result. In 18 reviews, the quality adjustment would have resulted in a different decision about the usefulness of the test.

Conclusions: Although reporting the results of quality assessment of individual studies is necessary in systematic reviews, reader wariness is warranted regarding claims that differences in methodological quality have been accounted for. Obstacles for adjusting for quality in metaanalyses are poor reporting of design features and patient characteristics and the relatively low number of studies in most diagnostic reviews.
Novel Biosensor–Based Analytic Device for the Detection of Anti–Double-Stranded DNA Antibodies
Authors: Buhl Alexander , Metzger Jochen H , Heegaard Niels H H , von Landenberg Philipp , Fleck Martin , Luppa Peter B
Published: December 2006

Background: Patients with systemic lupus erythematosus (SLE) develop a wide variety of serologic manifestations, including double-stranded DNA autoantibodies (anti-dsDNA). The determination of the potentially pathogenic autoantibodies is diagnostically relevant.

Methods: We developed a novel surface plasmon resonance (SPR) biosensor chip for studies of dsDNA and anti-dsDNA binding. A synthetic oligonucleotide was coupled to biotinylated human transferrin, hybridized with the complementary antistrand, and ligated with a human recombinant dsDNA fragment 233 bp in length. After surface immobilization of this antigenic construct, diluted sera from SLE patients and healthy donors were analyzed with the resulting SPR biosensor system.

Results: This SPR biosensor allowed specific detection of anti-dsDNA. In pilot experiments, sera from SLE patients were distinguished from control sera. We also confirmed the specificity of this biosensor by supplementing anti-dsDNA–positive sera with salmon sperm DNA, which blocked the surface binding of anti-dsDNA in a concentration-dependent manner.

Conclusions: An SPR biosensor monitors interactions in real time under homogeneous conditions, providing information about binding kinetics and affinities. Its applicability critically depends on the design of the solid-state surface of the sensor chips. Covalently immobilizing dsDNA as the antigen to the surface in a flow-through cell assured maximal stability for multiple serum injections and regeneration cycles. This technique, which adds a new analytic quality to existing methods, may be beneficial in the diagnosis and clinical monitoring of SLE.
Heterozygous parkin point mutations are as common in control subjects as in Parkinson's patients
Authors: Kay Denise M. , Moran Dawn , Moses Lina , Poorkaj Parvoneh , Zabetian Cyrus P. , Nutt John , Factor Stewart A. , Yu Chang‐En , Montimurro Jennifer S. , Keefe Robert G. , Schellenberg Gerard D. , Payami Haydeh
Published: December 2006

Objective

Homozygous or compound heterozygous parkin mutations cause juvenile parkinsonism. Heterozygous parkin mutations are also found in patients with typical Parkinson's disease (PD), but it is unclear whether a single “mutation” in a patient is related to disease or is coincidental, because the mutation frequency in control subjects is unknown. We present a comprehensive sequence analysis of parkin in control subjects.

Methods

A total of 302 patients and 301 control subjects were sequenced, and findings were replicated in 1,260 additional patients and 1,657 control subjects.

Results

Thirty‐four variants were detected, of which 21 were novel; 12 were polymorphisms and 22 were rare variants. Patients and control subjects did not differ in the frequency, type, or functional location of the variants. Even P437L, a common mutation thought to be pathogenic, was present in unaffected control subjects.

Interpretation

parkin point mutations are not exclusive to PD. The mere presence of a single point mutation in a patient, in the absence of a second mutation, should not be taken as a cause of disease unless corroborated by family data and functional studies. This study does not support the notion that heterozygous parkin sequence variants (mutations or polymorphisms) are risk factors for PD. Whether heterozygous dosage anomalies are associated with PD remains to be determined. Ann Neurol 2006
How to tweak a beak: molecular techniques for studying the evolution of size and shape in Darwin's finches and other birds
Authors: Schneider Richard A.
Published: December 2006

A flurry of technological advances in molecular, cellular and developmental biology during the past decade has provided a clearer understanding of mechanisms underlying phenotypic diversification. Building upon such momentum, a recent paper tackles one of the foremost topics in evolution, that is the origin of species‐specific beak morphology in Darwin's finches.1 Previous work involving both domesticated and wild birds implicated a well‐known signaling pathway (i.e. bone morphogenetic proteins) and one population of progenitor cells in particular (i.e. cranial neural crest), as primary factors for establishing beak size and shape. But these results were limited in their ability to explain fully the morphogenetic bases of patterned outgrowth. So in a quest to identify novel genes whose expression correlated with differences in beak anatomy among Darwin's finches, a DNA microarray approach was undertaken using tissues harvested from the Galápagos Islands. The results are striking and point to a protein called calmodulin, which is a mediator of cellular calcium signaling, as a key determinant of beak length. BioEssays 29: 1–6, 2007. © 2006 Wiley Periodicals, Inc.
Application of Residence Time Distribution for Measuring the Fluid Velocity and Dispersion Coefficient
Authors: Zhang T. W. , Wang T. F. , Wang J. F.
Published: December 2006

Most studies on residence time distribution (RTD) have focused on the tail of the RTD curve, and very little attention has been paid to the effect of white noise on the measured results. The aim of this work is to study the effect of white noise on the calculated parameters with different data processing methods. The anti‐disturbance abilities of the moment method and the least squares method are compared. The results show that the anti‐disturbance ability of the least squares method was better than that of the moment method. As a result of peak overlapping in the RTD curve of a loop reactor, the moment method cannot be used to calculate the fluid velocity and dispersion coefficient. Experiments show that the least squares method is still applicable in a loop reactor.
Thermodynamic Equilibrium Calculations for the Reforming of Coke Oven Gas with Gasification Gas
Authors: Li Y. B. , Xiao R. , Jin B. S.
Published: December 2006

Thermodynamic analyses of the reforming of coke oven gas with gasification gas for syngas were investigated as a function of coke oven gas‐to‐gasification gas ratio (1–3), oxygen‐to‐methane ratio (0–1.56), pressure (25–35 bar) and temperature (700–1100 °C). Thermodynamic equilibrium results indicate that the operating temperature should be approximately 1100 °C and the oxygen‐to‐methane ratio should be approximately 0.39, where about 80 % CH4and CO2can be converted at 30 bar. Increasing the operating pressure shifts the equilibrium toward the reactants (CH4and CO2); increasing the pressure from 25 to 35 bar decreases the conversion of CO2from 73.7 % to 67.8 %. The conversion ratio of CO2is less than that in the absence of O2. For a constant feed gas composition (7 % O2, 31 % gasification gas, and 62 % coke oven gas), a H2/CO ratio of about 2 occurs at temperatures of 950 °C and above. Pressure effects on the H2/CO ratio are negligible for temperatures greater than 750 °C. The steam produced has an effect on the hydrogen selectivity, but its mole fraction decreases with temperature; trace amounts of other secondary products are observed.
Residence Time Distribution in Tubular Joule Effect Heaters with and without Geometric Modifications
Authors: André C. , Boissier B. , Fillaudeau L.
Published: December 2006

In the food industry, heat treatment of highly viscous fluids in continuous processes is becoming more and more common, and the process should perform as a homogenous thermal treatment, in order to ensure quality and safety of the final product. To improve treatment homogeneity, geometric modifications can be used even in the laminar regime, to induce flow perturbation and mixing. The objectives of this work include: (i) Investigation of the residence time distribution (RTD) for industrial indirect Joule effect heaters (JEH), with smooth (ST) and modified (MT) tubes, (ii) Demonstration and quantification of the efficiency of the geometrical modifications, and (iii) Proposition of a single semi‐empirical model including the flow regime (10 < Re < 2000) and tube diameters (18 and 23 mm). The results obtained confirm that the simple Dispersed Plug Flow (DPF) model is not adaptable to small Reynolds numbers. Further analysis demonstrates that certain geometrical modifications improve the treatment homogeneity by increasing the plug flow contribution and reducing the value of the reduced variance. These beneficial effects increase when the Reynolds number is increased, the nominal diameter is reduced, and modified tubes are used. The proposed model enables the prediction of the RTD in JEH with an accurate degree of confidence.
Dimethylzinc‐Mediated, Enantioselective Synthesis of Propargylic Amines
Authors: Zani Lorenzo , Eichhorn Torsten , Bolm Carsten
Published: December 2006

A one‐pot, enantioselective synthesis of N‐aryl propargylic amines, using alkynylation reagents obtained from dimethylzinc and terminal acetylenes in combination with various aldehydes and o‐methoxyaniline as starting materials, has been developed. Enantiopure β‐amino alcohols derived from norephedrine were used as non‐covalent chiral auxiliaries, both in stoichiometric or substoichiometric amount. After optimization, propargylic amines were obtained in good to high yields (up to 93 %) and with moderate to high enantiomeric excesses (up to 97 % ee). The possibility to recover the chiral auxiliary after the reaction was demonstrated.
Analysis of color symbology from the perspective of cultural semiotics focused on Korean costume colors according to the cultural changes
Authors: Lee Jee Hyun , Kim Young‐In
Published: December 2006

The purpose of this study was to analyze the symbolization of colors as cultural codes, based on costume colors. In order to study the significance of colors in cultural changes, we carried out a quantitative analysis and interpreted it from the perspective of cultural semiotics. The range of this study was focused on Korean costume colors, over diverse diachronic stages of Korean culture. For this study 1535 color samples were collected, measured with a spectrophotometer, and analyzed quantitatively according their diachronic stages of origin. As a result, red, blue, and yellow were found to be the most frequently used colors during the Chosun Dynasty, a period based on Confucianism. These colors acted as cultural codes with cultural significance. During the Modern times pink, light blue, and black increased in frequency and represented the reception of western culture, the changing sex role of women in society, and utilitarianism. In these days, neutral colors and grayish tones of all colors are the most significant colors of high frequency. The use of such colors is closely related to industrialization, mechanization, functionalism, and the changes of women's sex roles in the societies. They are used as cultural codes, especially to emphasize a rational and masculine image rather than a feminine image. © 2006 Wiley Periodicals, Inc. Col Res Appl, 32, 71–79, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/col.20290
Protein crystal nucleation: Recent notions
Authors: Nanev Christo N.
Published: December 2006

The nucleation of protein crystals is reconsidered taking into account the specificity of the protein molecules. In contrast to the homogeneous surface properties of small molecules, the protein molecule surface is highly inhomogeneous. Over their surfaces proteins exhibit high anisotropic distribution of patches, which are able to form crystalline bonds, the crystallization patch representing only a small fraction of the total surface of the protein molecule. Therefore, an appropriate spatial orientation of the colliding protein molecules is required in order to create a crystalline cluster. This scenario decreases considerably the success ratio of the attempt frequency for crystal nucleation. On the other hand a heterogeneous nucleation of (protein) crystals may be accelerated due to the arrival on some support of under‐critical clusters that are formed in bulk solution; when arriving there they may acquire the property of critical nuclei. Thus, a plausible explanation of important peculiarities of protein crystal nucleation, as inferred from the experimental data, is suggested. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Growth and characterization of sulphamic acid single crystals grown by Sanakaranarayanan‐Ramasamy (SR) method
Authors: Lenin M. , Balamurugan N. , Ramasamy P.
Published: December 2006

By directional solidification, single crystal of Sulphamic acid (SA) was successfully grown from aqueous solution by Sankaranarayanan‐Ramasamy (SR) method. A vertically designed L‐bend was used to avoid the effect due to spurious nucleation. A vertical bottom‐seeded ampoule was used for the growth of single crystal. A seed crystal was mounted at the bottom of the ampoule. Sulphamic acid crystals of up to 40 mm in diameter and 60 mm in length have been grown with a growth up to 10 mm per day. The grown sulphamic acid single crystal was characterized using X‐ray powder diffraction analysis, Raman, FTIR, and optical transmission studies. The dielectric behaviour was measured in the frequency range of 1 kHz–10 MHz for the temperature ranges from 30 °C to 170 °C. The sulphamic acid single crystal was also grown by conventional method. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Transgene expression of prion protein induces crinophagy in intermediate pituitary cells
Authors: van Rosmalen Jos W.G. , Martens Gerard J.M.
Published: December 2006

The cellular form of the prion protein (PrPC) is a plasma membrane‐anchored glycoprotein whose physiological function is poorly understood. Here we report the effect of transgene expression of Xenopus PrPC fused to the C‐terminus of the green fluorescent protein (GFP‐PrPC) specifically in the neuroendocrine intermediate pituitary melanotrope cells of Xenopus laevis. In the transgenic melanotrope cells, the level of the prohormone proopiomelanocortin (POMC) in the secretory pathway was reduced when the cells were (i) exposed for a relatively long time to the transgene product (by physiologically inducing transgene expression), (ii) metabolically stressed, or (iii) forced to produce unfolded POMC. Intriguingly, although the overall ultrastructure was normal, electron microscopy revealed the induction of lysosomes taking up POMC secretory granules (crinophagy) in the transgenic melanotrope cells, likely causing the reduced POMC levels. Together, our results indicate that in neuroendocrine cells transgene expression of PrPC affects the functioning of the secretory pathway and induces crinophagy. © 2006 Wiley Periodicals, Inc. J Neurobiol 67: 81–96, 2007
Summary of ‘Inhaled corticosteroids versus sodium cromoglycate in children and adults with asthma’
Authors: Milne Andrea
Published: December 2006

This is a summary of a Cochrane review, published in this issue of EBCH, first published as: Guevara JP, Ducharme FM, Keren R, Nihtianova S, Zore J. Inhaled corticosteroids versus sodium cromoglycate in children and adults with asthma. Cochrane Database of Systematic Reviews 2006, Issue 2. Art. No.: CD003558. DOI: 10.1002/14651858.CD003558.pub2.

Further information for this Cochrane review is available in this issue of EBCH in the accompanying Expert Commentary and Characteristics and Key Findings Tables articles. Copyright © 2006 John Wiley & Sons, Ltd.
Summary of ‘Antibiotic prophylaxis for surgical introduction of intracranial ventricular shunts’
Authors: Milne Andrea
Published: December 2006

This is a summary of a Cochrane review, published in this issue of EBCH, first published as: Ratilal B, Costa J, Sampaio C. Antibiotic prophylaxis for surgical introduction of intracranial ventricular shunts. Cochrane Database of Systematic Reviews 2006, Issue 3. Art. No.: CD005365. DOI: 10.1002/14651858.CD005365.pub2.

Further information for this Cochrane review is available in this issue of EBCH in the accompanying Expert Commentary and Characteristics and Key Findings Tables articles. Copyright © 2006 John Wiley & Sons, Ltd.
Commentary on ‘Holding chambers (spacers) versus nebulisers for beta‐agonist treatment of acute asthma’
Authors: Osmond Martin H.
Published: December 2006

This is a commentary on a Cochrane review, published in this issue of EBCH, first published as: Cates CJ, Crilly JA, Rowe BH. Holding chambers (spacers) versus nebulisers for beta‐agonist treatment of acute asthma. Cochrane Database of Systematic Reviews 2006, Issue 2. Art. No.: CD000052. DOI: 10.1002/14651858.CD000052.pub2.

Further information for this Cochrane review is available in this issue of EBCH in the accompanying EBCH Summary and Characteristics and Key Findings Tables articles. Copyright © 2006 John Wiley & Sons, Ltd.
Commentary on ‘Inhaled corticosteroids versus sodium cromoglycate in children and adults with asthma’
Authors: Mellis Craig
Published: December 2006

This is a commentary on a Cochrane review, published in this issue of EBCH, first published as: Guevara JP, Ducharme FM, Keren R, Nihtianova S, Zorc J. Inhaled corticosteroids versus sodium cromoglycate in children and adults with asthma. Cochrane Database of Systematic Reviews 2006, Issue 2, Art. No.: CD003558. DOI: 10.1002/14651858.CD003558.pub2.

Further information for this Cochrane review is available in this issue of EBCH in the accompanying EBCH Summary and Characteristics and Key Findings Tables articles. Copyright © 2006 John Wiley & Sons, Ltd.
Characteristics and key findings for ‘Corticosteroid therapy for nephrotic syndrome in children’
Authors: van Dalen Elvira C. , Martin Offringa , Kremer Leontien C. M.
Published: December 2006

These are the characteristics and key findings for a Cochrane review, published in this issue of EBCH, first published as: Hodson EM, Knight JF, Willis NS, Craig JC. Corticosteroid therapy for nephrotic syndrome in children. Cochrane Database of Systematic Reviews 2005, Issue 1. Art. No.: CD001533. DOI: 10.1002/14651858.CD001533.pub3.

Further information for this Cochrane review is available in this issue of EBCH in the accompanying EBCH Summary and Expert Commentary articles. Copyright © 2006 John Wiley & Sons, Ltd.
Characteristics and key findings for ‘Antibiotics for community acquired pneumonia in children’
Authors: van Dalen Elvira C. , Martin Offringa , Kremer Leontien C. M.
Published: December 2006

These are the characteristics and key findings for a Cochrane review, published in this issue of EBCH, first published as: Kabra SK, Lodha R, Pandey RM. Antibiotics for community acquired pneumonia in children. Cochrane Database of Systematic Reviews 2006, Issue 3. Art. No.: CD004874. DOI: 10.1002/14651858.CD004874.pub2.

Further information for this Cochrane review is available in this issue of EBCH in the accompanying EBCH Summary and Expert Commentary articles. Copyright © 2006 John Wiley & Sons, Ltd.
Renal failure and bacterial infections in patients with cirrhosis: Epidemiology and clinical features
Authors: Fasolato Silvano , Angeli Paolo , Dallagnese Lucia , Maresio Giulio , Zola Erika , Mazza Elena , Salinas Freddy , Donà Silvio , Fagiuoli Stefano , Sticca Antonietta , Zanus Giacomo , Cillo Umberto , Frasson Ilaria , Destro Carla , Gatta Angelo
Published: December 2006

The aim of the study was to investigate the prevalence and clinical course of renal failure that was induced by the various types of bacterial infections in patients with cirrhosis and ascites. Three hundred and nine patients, who were consecutively admitted to the 3 major hospitals of Padova, Italy, during the first 6 months of 2005, were studied prospectively. Of these, 233 patients (75.4%) had evidence of ascites. In 104 patients with cirrhosis and ascites (44.6%) a bacterial infection was diagnosed. A bacterial infection-induced renal failure was observed in 35 of 104 patients (33.6%). The prevalence of renal failure was higher in biliary or gastrointestinal tract infections and in spontaneous bacterial peritonitis (SBP) and in than in other types of infections. In addition, the progressive form of renal failure was only precipitated by biliary or gastrointestinal tract infections, SBP, and urinary tract infections (UTI). In a multivariate analysis only MELD score (

P

= 0.001), the peak count of neutrophil leukocyte in blood (

P

= 0.04), and the lack of resolution of infection (

P

= 0.03) had an independent predictive value on the occurrence of renal failure.

Conclusion

: The results of the study show that the development of bacterial-induced renal failure in patients with cirrhosis and ascites is related to the MELD score, and to both the severity and the lack of resolution of the infection. A progressive form of renal failure occurs only as a consequence of biliary or gastrointestinal tract infections, SBP, and UTI. (Hepatology 2007;45:223–229.)
Hepatitis C virus eradication in intravenous drug users maintained with subcutaneous naltrexone implants
Authors: Jeffrey Gary P. , MacQuillan Gerry , Chua Fern , Galhenage Sam , Bull Judith , Young Emma , Hulse Gary , O'Neil George
Published: December 2006

The effectiveness of HCV antiviral therapy in patients who have undergone recent drug dependency treatment and continue to inject drugs sporadically is presently not clear. Patients attending a community-based drug rehabilitation and naltrexone implant clinic from October 2002 until March 2005 were screened for HCV infection and if positive offered further assessment and treatment with interferon and ribavirin therapy. The first 50 patients to commence HCV therapy and complete at least 6 months follow-up were prospectively studied. ETR response (HCV PCR negative) was 34/50 (68%) and SVR 6 months post-treatment was 31/50 (62%). Viral eradication was maintained in those 22 patients that have had 12 months or more post-treatment follow-up. Eleven (22%) patients stopped therapy early due to side effects or poor compliance. Only two patients with an ETR likely reinfected due to unsafe injection practices. One was re-treated and achieved an SVR. Of the patients achieving a 6-month SVR, 17 of 31 patients reported no further IDU and 13 of 31 patients occasional IDU during treatment and this was maintained after HCV treatment cessation. 46% of patients received antidepressant and/or antipsychotic medication during treatment.

Conclusion:

This study of HCV treatment in a community-based subcutaneous naltrexone implant clinic found antiviral therapy resulted in a 62% SVR. This result is comparable to that reported in hospital-based clinics in non-IDU patients. The side effect profile and compliance was also similar. HCV antiviral therapy should be offered to this large and currently under treated group. (Hepatology 2007;45:111–117.)
Prostaglandin I2 and E2 mediate the protective effects of cyclooxygenase-2 in a mouse model of immune-mediated liver injury
Authors: Yin Hao , Cheng Linling , Langenbach Robert , Ju Cynthia
Published: December 2006

Studies of the molecular and cellular mechanisms of concanavalin A (ConA)-induced liver injury have provided important knowledge on the pathogenesis of many liver diseases involving hepatic inflammation. However, studies identifying hepato-protective factors based on the mechanistic understanding of this model are lacking. Evidence suggests that certain prostaglandin (PG) products of cyclooxygenase (COX)-1 and COX-2 provide important anti-inflammatory and cytoprotective functions in some pathophysiological states. In the present study, we demonstrate a protective role of COX-2 derived PGs in ConA-induced liver injury. COX-2−/− mice developed much more severe liver damage upon ConA treatment compared with wild-type and COX-1−/− mice. Treatment of COX-2−/− mice with misoprostol (a PGE1/2 analog) or beraprost (a PGI2 analog) significantly decreased ConA-induced liver injury. Data from both

in vivo

and

in vitro

experiments demonstrated that misoprostol and beraprost acted directly on hepatic leukocytes, including natural killer (NK)T and T cells, and down-regulated their production of interferon (IFN)-γ, which are critical in mediating ConA-induced tissue damage. Collectively, the results provide strong evidence that the protective effects of COX-2 within the liver are mediated through the production of PGE2 and PGI2, which exert anti-inflammatory functions. These findings suggest that COX-2-derived PGs may have great therapeutic potentials in treating patients with inflammatory liver diseases. (Hepatology 2007;45:159–169.)