bluuebunny/crossref_metadata_2025 huggingface dataset:
Arcuate Glucagon-Like Peptide 1 Receptors Regulate Glucose Homeostasis but Not Food Intake
Authors: Sandoval Darleen A. , Bagnol Didier , Woods Stephen C. , D'Alessio David A. , Seeley Randy J.
Published: May 2008

OBJECTIVE—Glucagon-like peptide-1 (GLP-1) promotes glucose homeostasis through regulation of islet hormone secretion, as well as hepatic and gastric function. Because GLP-1 is also synthesized in the brain, where it regulates food intake, we hypothesized that the central GLP-1 system regulates glucose tolerance as well.

RESEARCH DESIGN AND METHODS—We used glucose tolerance tests and hyperinsulinemic-euglycemic clamps to assess the role of the central GLP-1 system on glucose tolerance, insulin secretion, and hepatic and peripheral insulin sensitivity. Finally, in situ hybridization was used to examine colocalization of GLP-1 receptors with neuropeptide tyrosine and pro-opiomelanocortin neurons.

RESULTS—We found that central, but not peripheral, administration of low doses of a GLP-1 receptor antagonist caused relative hyperglycemia during a glucose tolerance test, suggesting that activation of central GLP-1 receptors regulates key processes involved in the maintenance of glucose homeostasis. Central administration of GLP-1 augmented glucose-stimulated insulin secretion, and direct administration of GLP-1 into the arcuate, but not the paraventricular, nucleus of the hypothalamus reduced hepatic glucose production. Consistent with a role for GLP-1 receptors in the arcuate, GLP-1 receptor mRNA was found to be expressed in 68.1% of arcuate neurons that expressed pro-opiomelanocortin mRNA but was not significantly coexpressed with neuropeptide tyrosine.

CONCLUSIONS—These data suggest that the arcuate GLP-1 receptors are a key component of the GLP-1 system for improving glucose homeostasis by regulating both insulin secretion and glucose production.
Impact of Oxidative Stress and Peroxisome Proliferator–Activated Receptor γ Coactivator-1α in Hepatic Insulin Resistance
Authors: Kumashiro Naoki , Tamura Yoshifumi , Uchida Toyoyoshi , Ogihara Takeshi , Fujitani Yoshio , Hirose Takahisa , Mochizuki Hideki , Kawamori Ryuzo , Watada Hirotaka
Published: May 2008

OBJECTIVE—Recent studies identified accumulation of reactive oxygen species (ROS) as a common pathway causing insulin resistance. However, whether and how the reduction of ROS levels improves insulin resistance remains to be elucidated. The present study was designed to define this mechanism.

RESEARCH DESIGN AND METHODS—We investigated the effect of overexpression of superoxide dismutase (SOD)1 in liver of obese diabetic model (db/db) mice by adenoviral injection.

RESULTS— db/db mice had high ROS levels in liver. Overexpression of SOD1 in liver of db/db mice reduced hepatic ROS and blood glucose level. These changes were accompanied by improvement in insulin resistance and reduction of hepatic gene expression of phosphoenol-pyruvate carboxykinase and peroxisome proliferator–activated receptor γ coactivator-1α (PGC-1α), which is the main regulator of gluconeogenic genes. The inhibition of hepatic insulin resistance was accompanied by attenuation of phosphorylation of cAMP-responsive element-binding protein (CREB), which is a main regulator of PGC-1α expression, and attenuation of Jun NH2-terminal kinase (JNK) phosphorylation. Simultaneously, overexpression of SOD1 in db/db mice enhanced the inactivation of forkhead box class O1, another regulator of PGC-1α expression, without the changes of insulin-induced Akt phosphorylation in liver. In hepatocyte cell lines, ROS induced phosphorylation of JNK and CREB, and the latter, together with PGC-1α expression, was inhibited by a JNK inhibitor.

CONCLUSIONS—Our results indicate that the reduction of ROS is a potential therapeutic target of liver insulin resistance, at least partly by the reduced expression of PGC-1α.
Common Variation in the Fat Mass and Obesity-Associated (FTO) Gene Confers Risk of Obesity and Modulates BMI in the Chinese Population
Authors: Chang Yi-Cheng , Liu Pi-Hua , Lee Wei-Jei , Chang Tien-Jyun , Jiang Yi-Der , Li Hung-Yuan , Kuo Shan-Shan , Lee Kuang-Chin , Chuang Lee-Ming
Published: May 2008

OBJECTIVE— Genetic variants in the fat mass and obesity-associated (FTO) gene have been linked with obesity and type 2 diabetes in European populations. We aimed to test the role of FTO genetic variants in obesity and type 2 diabetes in the Chinese population.

RESEARCH DESIGN AND METHODS— We genotyped 19 single-nucleotide polymorphisms (SNPs) spanning from the 3′ end of the neighboring RPGRIP1L gene to the 5′ flanking region of the FTO gene. We analyzed their associations with obesity (638 case and 1,610 control subjects), type 2 diabetes (759 case and 784 control subjects), and obesity-related traits in nondiabetic subjects.

RESULTS— Among the 19 SNPs, the rs9939609 A allele was strongly associated with obesity (P = 7.0 × 10−4) and BMI (P = 0.0024) in the Chinese population. The odds ratio for obesity was 2.60 (95% CI 1.24–5.46) (P = 0.011) for the AA genotype and 1.32 (1.05–1.66) (P = 0.018) for the AT genotype compared with the TT genotype. Each additional copy of the rs9936609 A allele was associated with a BMI increase of ∼0.37 kg/m2. The rs9939609 A allele was substantially less common in the Chinese population than in the European population (12.6 vs. 45%). We did not find significant associations of the 19 SNPs with type 2 diabetes or other obesity-related traits.

CONCLUSIONS— Genetic variation in the FTO gene is strongly associated with obesity and BMI in the Chinese population. The risk variant is less common in the Chinese population, but its effect size on BMI is comparable with that in the European population.
Biocompatibility of Materials in Medical Devices
Authors: Frederick Silver
Published: May 2008

Medical devices are used for a variety of functions in humans. This review elaborates on the types of tests used to evaluate biocompatibility of the interactions between man‐made medical devices and host tissues and organs. The outcome of the response depends on the site of implantation, the species of the host, the genetic makeup of the host, the sterility of the implant, and the effect the device has on biological processes. Biological processes involved in host tissue responses to implantable medical devices reflect activation of a series of cascades that require blood proteins or other components found in the blood.

Two types of regulatory approvals for medical devices exist in the United States, 510(k) notification and premarket approval (PMA). The specific tests required prior to regulatory approval vary with the type of device and application; however, some general testing is usually recommended. Normally, animal testing is conducted to demonstrate that a medical device is safe, and when implanted in humans the device will reduce, alleviate, or eliminate the possibility of adverse medical reactions or conditions. The American Society for Testing and Materials (ASTM) as well as the International Organization for Standardization (ISO) publishes standards for testing medical devices. The recommended tests include culture cytotoxicity, skin irritation, short‐term intramuscular implantation, short‐term subcutaneous implantation, blood coagulation, long‐term implantation, mucous membrane irritation, systemic injection, sensitization assays, and mutagenicity testing.
Calcium Pump, Chemistry of
Authors: Anthonisen Anne Nyholm , Andersen Jens Peter
Published: May 2008

Sarco(endo)plasmic reticulum Ca2+‐ATPase (SERCA) transports Ca2+ions against a concentration gradient using energy derived by the hydrolysis of ATP. SERCA forms an aspartyl phosphorylated intermediate, which is acid stable, thus enabling studies of the reaction mechanism. Methods have been established for a detailed functional analysis of mutants, allowing definition of the roles of the individual amino acid residues in the partial reaction steps, and the mutational studies can now be correlated with the positions of the residues in crystal structures of SERCA in various conformational states. Here, we use the glutamine mutant of Glutamate 183 as an example of the methods and analyses. This mutant exhibits a block of the dephosphorylation of the E2P intermediate, but it is little affected in the E1 state, which is consistent with a key role for Glu183 in positioning the attacking water molecule during the hydrolysis of the acyl phosphate bond in the E2P phosphoenzyme.
Cytosolic Glycosylated Proteins, Chemistry of
Authors: A. Toleman Clifford , E. Kudlow Jeffrey
Published: May 2008

O
‐GlcNAcylation is a prevalent posttranslational modification that occurs when a molecule of the monosaccharide
N
‐acetylglucosamine (GlcNAc) is adjoined to a serine or a threonine residue of a cellular protein. This modification can influence a protein in many of the same ways that a serine or threonine phosphorylation can. In addition, much like the kinases and phosphatases involved in phosphorylation/dephosphorylation, unique enzymes are responsible for the addition and removal of
O
‐GlcNAc modifications, with an
O
‐GlcNAc transferase that catalyzes the addition and an
O
‐GlcNAcase that is responsible for the removal. This review will give a summate description of the diverse biochemical roles that this
O
‐GlcNAcylation can play on individual proteins, and on whole animal systems, and will detail the current understanding of the enzymes involved in its maintenance. Finally, we discuss here the recent advances that have been made in the development of tools to study
O
‐GlcNAcylation.
Hypoxic Response and Associated Diseases
Authors: Emily Flashman , Christoph Loenarz , Schofield Christopher J.
Published: May 2008

Animals must respond efficiently to changes in oxygen levels. This response is achieved via oxygen‐dependent regulation of a heterodimeric hypoxia‐inducible transcription factor (HIF), which enables upregulation of genes that assist in the hypoxic response. Posttranslational hydroxylation of the HIF‐α subunit at either of two conserved prolyl residues enables binding to the von Hippel–Lindau protein elongin C/B complex that targets HIF‐α for degradation via the ubiquitin proteasome pathway. Hydroxylation of an asparaginyl residue in the C‐terminal transcriptional activation domain of HIF‐α blocks its interaction with the transcriptional coactivator p300. The HIF prolyl and asparaginyl hydroxylases are oxygen dependent; therefore, their regulation of HIF directly links changes in oxygen concentration and the physiological response to hypoxia. The hypoxic response is implicated in a range of disease states, including cancer, ischemia, and heart disease. Manipulation of the HIF system for therapeutic advantage is therefore an area of medicinal interest.
Nitric Oxide: Biological Targets
Authors: Derbyshire Emily R. , Marletta Michael A.
Published: May 2008

Nitric oxide (NO) is an essential signaling molecule for many eukaryotic organisms. NO is producedin vivoby the enzyme nitric oxide synthase (NOS) from the amino acidL‐arginine. The apolar gas readily diffuses across cell membranes, where it binds to the heme of soluble guanylate cyclase (sGC), the principle NO receptor. Once activated, sGC converts GTP to cGMP at a rate that is several‐hundred–fold above the basal level. This NO/cGMP signaling cascade modulates several physiologic processes including vasodilation, platelet aggregation, and neurotransmission. Although the cGMP‐dependent affects of NO remain active areas of research, additional cGMP‐independent responses to NO also are being investigated. Endogenous levels of NO can modulate protein function byS‐nitrosation, a covalent modification that has been implicated in the transcriptional regulation of genes involved in the immune response and in apoptosis.
Locked Nucleic Acids
Authors: Størling Zenia M. , Koch Troels
Published: May 2008

The intensive research and development of antisense oligonucleotides in the past decades has refined our knowledge of this class of molecules, and they are now recognized as potent reagents for gene‐target validation and therapeutic uses. Within this field, a very promising class is locked nucleic acid (LNA). In recent years, the number of applications for LNA in basic research, molecular diagnostics, and therapeutics has expanded continuously. In this article, the general biophysical, biochemical, and pharmacological properties of LNA will be summarised. The ability of LNA oligonucleotides to target both coding and noncoding RNAs effectively and specifically via different modes of action will be discussed. Several LNA oligonucleotides have completed preclinical toxicology and are now tested in clinical trials. The status of one drug candidate will be presented briefly at the end of the article.
Translational Recoding
Authors: Osborne Edith M. , Noren Christopher J.
Published: May 2008

The limitation of a triplet code with only four bases from which to choose and the size limitation of viral genomes has placed evolutionary pressure on translational coding. Organisms and viruses have developed a variety of methods of translational recoding, including codon reassignment and frameshifting, temporarily altering the canonical reading of mRNA to meet their needs. A translational recoding event can be caused by alterations in the mRNA and/or the tRNA and may even necessitate specific ribosomal elongation factors. Scientists also desire to alter the genetic code by manipulation of natural recoding events and by exploitation of artificial genetic code expansion.
Two‐ and Three‐Hybrid Systems
Authors: Gestwicki Jason E. , Kumar Anuj
Published: May 2008

One goal of chemical biology is to document and understand the macromolecular interactions that take place in the cell. In this review, we discuss the classic yeast two‐hybrid method (and its derivatives) and how this method continues to provide insight into the number of protein–protein partnerships in a cell. In turn, these platforms have been adapted to explore a variety of interactions, such as those between proteins and small molecules. These systems collectively are called three‐hybrid assays, and they provide new opportunities for the discovery of potential binding pairs. However, two‐ and three‐hybrid assays also have significant disadvantages, such as incomplete coverage and high rates of false positives. With these issues in mind, we discuss emerging ways of minimizing the impact of these limitations using microarrays and mass spectrometry. Finally, chemical probes related to the three‐hybrid concept are going beyond observation and providing active, rational control over individual protein–protein contacts. In these systems, bifunctional compounds are used to homo‐ or heterodimerize target proteins reversibly, thus altering their colocalization. By purposefully controlling protein–protein contacts, these chemical dimerization methods have progressed beyond observation and towards synthetic manipulation of protein function.
Naturally Occurring Peptide Hormones and Neurotransmitters: Synthesis
Authors: Liu Zhihua , Hruby Victor J.
Published: May 2008

How to synthesize biologically active polypeptides chemically has long been an important challenge for many fields in chemistry and biology. In the past, the development of solution‐phase and solid‐phase synthesis techniques has made it possible to synthesize large molecules like peptides with molecular weights up to 10,000. The purpose of this review is to provide an overview of how to prepare natural bioactive peptides synthetically. Because of space limitations, this review concentrates on peptide hormones and neurotransmitters.
Highly Practical “Ligand‐Free‐Like” Copper‐Catalyzed N‐Arylation of Azoles in Lower Nitrile Solvents
Authors: Zhu Rui , Xing Lixin , Wang Xinyan , Cheng Chuanjie , Su Deyong , Hu Yuefei
Published: May 2008

In lower nitrile solvents, the N‐arylation of azoles with aryl halides was achieved efficiently in the presence of copper powder without any additional ligands. Thus, the first nitrile type of monodentate ligand‐mediated, “ligand‐free‐like” copper‐catalyzed N‐arylation procedure was established.
Reactivity of Electrogenerated N‐Heterocyclic Carbenes in Room‐Temperature Ionic Liquids. Cyclization to 2‐Azetidinone Ring via C‐3/C‐4 Bond Formation
Authors: Feroci Marta , Chiarotto Isabella , Orsini Monica , Sotgiu Giovanni , Inesi Achille
Published: May 2008

The intrinsic chemistry of imidazolium‐based room‐temperature ionic liquids, related to the acidity of the C‐2 imidazolium cation, can be modified via cathodic cleavage of the C‐2/hydrogen bond. N‐Heterocyclic carbenes, electrogenerated by electrolysis of imidazolium‐based room‐temperature ionic liquids, are stable bases that are strong enough to deprotonate bromoamides 1a–k yielding the azetidin‐2‐one ring via C‐3/C4 bond formation. The electrosynthesis of β‐lactams 2a–k has been achieved under mild conditions, elevated yields and avoiding the use of toxic, volatile, molecular solvents.
Catalytic Enantioselective Hydrophosphonylation of Aldehydes and Imines
Authors: Merino Pedro , Marqués‐López Eugenia , Herrera Raquel P.
Published: May 2008

In this review, recent advances in catalytic asymmetric hydrophosphonylation of aldehydes and imines are discussed. We also summarize several proposed mechanisms for the different possibilities of asymmetric induction and the application of this catalytic methodology to the enantioselective synthesis of α‐amino and α‐hydroxy phosphonates. A variety of metal‐based chiral catalysts as well as several organic catalysts have been exploited as suitable systems for the preparation of enantiomerically pure phosphonates. The recent evolution and future trends of those and other catalytic systems are described.
Female monozygotic twins discordant for hemophilia A due to nonrandom X‐chromosome inactivation
Authors: Bennett Carolyn M. , Boye Eileen , Neufeld Ellis J.
Published: May 2008

We describe monozygotic female twins discordant for hemophilia A, born to a carrier mother and normal father. Affected twin A presented at age 1 year with excessive bruising and factor VIII procoagulant activity (FVIII:C) of less than 1% of normal. Twin B is an asymptomatic carrier with FVIII:C level of 42%. Peripheral blood DNA was tested for X‐chromosome inactivation (methylation) patterns of the X‐linked human androgen receptor gene, comparing the twins' patterns to parental. Twin A showed nonrandom inactivation skewed toward the paternal X, whereas twin B showed random X‐inactivation. This is the first reported case of discordance for hemophilia A between female monozygotic twins. Am. J. Hematol., 2008. © 2008 Wiley‐Liss, Inc.
Old Age and the Hepatic Sinusoid
Authors: Le Couteur David G. , Warren Alessandra , Cogger Victoria C. , Smedsrød Bård , Sørensen Karen K. , De Cabo Rafael , Fraser Robin , Mccuskey Robert S.
Published: May 2008

Morphological changes in the hepatic sinusoid with old age are increasingly recognized. These include thickening and defenestration of the liver sinusoidal endothelial cell, sporadic deposition of collagen and basal lamina in the extracellular space of Disse, and increased numbers of fat engorged, nonactivated stellate cells. In addition, there is endothelial up‐regulation of von Willebrand factor and ICAM‐1 with reduced expression of caveolin‐1. These changes have been termed age‐related pseudocapillarization. The effects of old age on Kupffer cells are inconsistent, but impaired responsiveness is likely. There are functional implications of these aging changes in the hepatic sinusoid. There is reduced sinusoidal perfusion, which will impair the hepatic clearance of highly extracted substrates. Blood clearance of a variety of waste macromolecules takes place in liver sinusoidal endothelial cells (LSECs). Previous studies indicated either that aging had no effect, or reduced the endocytic capacity of LSECs. However, a recent study in mice showed reduced endocytosis in pericentral regions of the liver lobules. Reduced endocytosis may increase systemic exposure to potential harmful waste macromolecules such as advanced glycation end products Loss of fenestrations leads to impaired transfer of lipoproteins from blood to hepatocytes. This provides a mechanism for impaired chylomicron remnant clearance and postprandial hyperlipidemia associated with old age. Given the extensive range of substrates metabolized by the liver, age‐related changes in the hepatic sinusoid and microcirculation have important systemic implications for aging and age‐related diseases. Anat Rec, 291:672–683, 2008. © 2008 Wiley‐Liss, Inc.
Functional Anatomy of Normal Bile Ducts
Authors: Strazzabosco Mario , Fabris Luca
Published: May 2008

The biliary tree is a complex network of conduits that begins with the canals of Hering and progressively merges into a system of interlobular, septal, and major ducts which then coalesce to form the extrahepatic bile ducts, which finally deliver bile to the gallbladder and to the intestine. The biliary epithelium shows a morphological heterogeneity that is strictly associated with a variety of functions performed at the different levels of the biliary tree. In addition to funneling bile into the intestine, cholangiocytes (the epithelial cells lining the bile ducts) are actively involved in bile production by performing both absorbitive and secretory functions. More recently, other important biological properties restricted to cholangiocytes lining the smaller bile ducts have been outlined, with regard to their plasticity (i.e., the ability to undergo limited phenotypic changes), reactivity (i.e., the ability to participate in the inflammatory reaction to liver damage), and ability to behave as liver progenitor cells. Functional interactions with other branching systems, such as nerve and vascular structures, are crucial in the modulation of the different cholangiocyte functions. Anat Rec, 291:653–660, 2008. © 2008 Wiley‐Liss, Inc.
Hemodynamic Changes in Splanchnic Blood Vessels in Portal Hypertension
Authors: Colle Isabelle , Geerts Anja M. , Van Steenkiste Christophe , Van Vlierberghe Hans
Published: May 2008

Portal hypertension (PHT) is associated with a hyperdynamic state characterized by a high cardiac output, increased total blood volume, and a decreased splanchnic vascular resistance. This splanchnic vasodilation is a result of an important increase in local and systemic vasodilators (nitric oxide, carbon monoxide, prostacyclin, endocannabinoids, and so on), the presence of a splanchnic vascular hyporesponsiveness toward vasoconstrictors, and the development of mesenteric angiogenesis. All these mechanisms will be discussed in this review. To decompress the portal circulation in PHT, portosystemic collaterals will develop. The presence of these portosystemic shunts are responsible for major complications of PHT, namely bleeding from gastrointestinal varices, encephalopathy, and sepsis. Until recently, it was accepted that the formation of collaterals was due to opening of preexisting vascular channels, however, recent data suggest also the role of vascular remodeling and angiogenesis. These points are also discussed in detail. Anat Rec, 291:699–713, 2008. © 2008 Wiley‐Liss, Inc.
Lymph Circulation in the Liver
Authors: Ohtani Osamu , Ohtani Yuko
Published: May 2008

The liver produces a large amount of lymph, which is estimated to be 25 to 50 % of lymph flowing through the thoracic duct. The hepatic lymphatic system falls into three categories depending on their locations: portal, sublobular, and superficial lymphatic vessels. It is suggested that 80 % or more of hepatic lymph drains into portal lymphatic vessels, while the remainder drains through sublobular and capsular lymphatic vessels. The hepatic lymph primarily comes from the hepatic sinusoids. Our tracer studies, together with electron microscopy, show many channels with collagen fibers traversing through the limiting plate and connecting the space of Disse with the interstitial space either in the portal tracts, or around the sublobular veins. Fluid filtered out of the sinusoids into the space of Disse flows through the channels traversing the limiting plate either independently of blood vessels or along blood vessels and enters the interstitial space of either portal tract or sublobular veins. Fluid in the space of Disse also flows through similar channels traversing the hepatocytes intervening between the space of Disse and the hepatic capsule and drains into the interstitial space of the capsule. Fluid and migrating cells in the interstitial space pass through prelymphatic vessels to finally enter the lymphatic vessels. The area of the portal lymphatic vessels increases in liver fibrosis and cirrhosis and in idiopathic portal hypertension. Lymphatic vessels are abundant in the immediate vicinity of the hepatocellular carcinoma (HCC) and liver metastasis. HCCs expressing vascular endothelial growth factor‐C are more liable to metastasize, indicating that lymphangiogenesis is associated with their enhanced metastasis. Anat Rec, 291:643–652, 2008. © 2008 Wiley‐Liss, Inc.
Hepatic Microcirculation in Fatty Liver Disease
Authors: Farrell Geoff C. , Teoh N.C. , Mccuskey R.S.
Published: May 2008

Nonalcoholic fatty liver disease (NAFLD), the most common cause of steatosis, is associated with visceral obesity and insulin resistance. With more severe risk factors (obesity, type 2 diabetes [T2D], metabolic syndrome), steatosis may be complicated by hepatocellular injury and liver inflammation (steatohepatitis or NASH). NASH can lead to perisinusoidal fibrosis and cirrhosis. Fat‐laden hepatocytes are swollen, and in steatohepatitis, further swelling occurs due to hydropic change (ballooning) of hepatocytes to cause sinusoidal distortion, as visualized by in vivo microscopy, reducing intrasinusoidal volume and microvascular blood flow. Involvement of other cell types (sinusoidal endothelial cells, Kupffer cells, stellate cells) and recruitment of inflammatory cells and platelets lead to dysregulation of microvascular blood flow. In animal models, the net effect of such changes is a marked reduction of sinusoidal space (∼50% of control), and a decrease in the number of normally perfused sinusoids. Such microvascular damage could accentuate further liver injury and disease progression in NASH. The fatty liver is also exquisitely sensitive to ischemia‐reperfusion injury, at least partly due to the propensity of unsaturated fatty acids to undergo lipid peroxidation in the face of reactive oxygen species (ROS). This has important clinical consequences, particularly limiting the use of fatty donor livers for transplantation. In this review, we discuss available data about the effects of steatosis and steatohepatitis on the hepatic microvascular structure and sinusoidal blood flow, highlighting areas for future investigation. Anat Rec, 291:684–692, 2008. © 2008 Wiley‐Liss, Inc.
Resistance and the underlife: Informal written literacies and their relationship to human information behavior
Authors: Trace Ciaran B.
Published: May 2008

This article presents findings from a research study (Trace, 2004) that looked at a particular aspect of human information behavior: children's information creation in a classroom setting. In the portion of the study described here, naturalism and ethnomethodology are used as theoretical frameworks to investigate informal documents as an information genre. Although previous studies have considered the role of informal documents within the classroom, little sustained attention has been paid to pre‐adolescents, particularly in terms of how they create unofficial or vernacular literacies both to navigate their growing awareness of the formal (albeit sometimes “hidden”) curriculum and, on occasion, to subvert it, positing an alternative economy that itself can be “hidden” via surreptitious use of informal documents. Making explicit the ties that exist between these objects and the worlds in which they are embedded demonstrates that informal documents hold a particular relevance for children within this social context (Garfinkel & Bittner, 1999). Furthermore, this article demonstrates that an ethnomethodologically informed viewpoint of information creation brings a level of dignity and determination to an individual's human information behavior, allowing us to appreciate the human ability to recontextualize or reenvisage sanctioned or official information genres to meet our own needs and purposes.
The structure of Web‐based information systems satisfaction: Testing of competing models
Authors: Cheung Christy M.K. , Lee Matthew K.O.
Published: May 2008

User satisfaction has become one of the most important measures of the success or effectiveness of information systems (IS). In the current study, the dimensionality of Web‐based information systems (WIS) satisfaction was first examined. Two composite latent variable models with factor‐order structures were then empirically tested and compared to describe the relationships among observable variables concerned with WIS satisfaction. Using data from a sample of 515 university students, a third‐order composite latent variable model was retained based on statistical and theoretical criteria. At the third‐order level, WIS satisfaction is determined by two second‐order constructs: Web information satisfaction and Web system satisfaction. Web information satisfaction is determined by understandability, reliability, and usefulness, while Web system satisfaction is determined by access, usability, and navigation. Overall, the model provides a good fit to the data and is theoretically valid, reflecting logical consistency. Implications of the current investigation for practice and research are provided.
Percentage of high‐grade carcinoma as a prognostic indicator in patients with renal cell carcinoma
Authors: Serrano Maria F. , Katz Matthew , Yan Yan , Kibel Adam S. , Humphrey Peter A.
Published: May 2008

BACKGROUND.

The prognostic value of Fuhrman nuclear grade for patients with renal cell carcinoma has been well‐characterized. However, to the authors' knowledge, the prognostic significance of the amount of high‐grade renal cell carcinoma has not been previously analyzed.

METHODS.

The authors identified 898 consecutive renal cell carcinoma cases treated with nephrectomy between 1989 and 2003. Histopathologic features that were captured based on re‐review of all slides included histologic type, pathologic stage, conventional Fuhrman grade, and percentage of Fuhrman grade 3 and 4 carcinoma, as ascertained by visual inspection of histologic slides. The clinical endpoints were metastasis‐free survival, cancer‐specific survival, and overall survival.

RESULTS.

Kaplan‐Meier analysis demonstrated that both conventional Fuhrman grading and the percentage of Fuhrman grade 3 and 4 carcinoma were highly correlated with all 3 measures of patient survival (P < .0001). The creation of 3 categories of the percentage of Fuhrman grade 3 and 4 carcinoma (0%, 1–50%, and 51–100%) generated distinctly separate survival curves. On Cox proportional hazards multivariate analysis, TNM stage, tumor size, and the percentage of Fuhrman grade 3 and 4 carcinoma were all found to be significantly associated with all 3 types of patient survival (all P values <.05).

CONCLUSIONS.

The determination of the percentage of renal cell carcinoma that is 0%, 1% to 50%, or 51% to 100% high Fuhrman grade 3 and 4 is a simple and powerful measurement of patient outcome after surgery that provides additional prognostic information beyond stage, tumor size, and conventional Fuhrman grade. This prognostic information could be useful in the stratification of patients into prognostic groups for the development of more individualized follow‐upschedules and for enrollment into clinical trials. Cancer 2008. © 2008 American Cancer Society.
Young age may predict a better outcome for children with diffuse pontine glioma
Authors: Broniscer Alberto , Laningham Fred H. , Sanders Robert P. , Kun Larry E. , Ellison David W. , Gajjar Amar
Published: May 2008

BACKGROUND.

Because diffuse pontine glioma (DPG) is rare among young children, the outcome of affected patients is unknown.

METHODS.

The authors reviewed clinical and radiologic characteristics of all children aged <3 years with DPG who were evaluated at their institution. Inclusion followed standard magnetic resonance imaging criteria for the diagnosis of DPG.

RESULTS.

The median age at diagnosis in 10 patients was 2.2 years (range, 0.8–2.7 years). The median interval between the onset of symptoms and diagnosis was 2.5 months. All patients presented with cranial nerve palsy with (n = 7) or without (n = 3) other neurologic deficits attributable to brainstem involvement. All patients had pons‐based tumors involving >50% of this brainstem segment. Histologic confirmation was attempted in 2 patients who had atypical radiologic features at diagnosis. Four patients initially were observed only. All patients received therapy, which consisted of radiation therapy (RT) (n = 2), RT and chemotherapy (n = 6), or chemotherapy only (n = 2). Four patients died of tumor progression after a median of 0.7 years (range, 0.5–3.7 years). Six patients have survived for a median of 2.3 years (range, 0.9–8 years). The 3‐year progression‐free and overall survival rates were 45% ± 19% and 69% ± 19%, respectively.

CONCLUSIONS.

Children aged <3 years with DPG potentially may fare better than older patients with the same diagnosis despite the use of similar therapy. The current results suggested that DPG in younger children may be distinct biologically from similar tumors in older age groups. Cancer 2008. © 2008 American Cancer Society.
Local circuitry in the anterior caudal lobe of the mormyrid cerebellum: A study of intracellular recording and labeling
Authors: Zhang Yueping , Han Phil F. , Han Victor Z.
Published: May 2008

Sagittal view of a Purkinje cell with symmetric dendritic tree from the anterior caudal lobe of the cerebellum of a mormyrid fish (Gnathonemus petersii). The cell was filled with neurobiotin in an in vitro slice preparation and tracer was revealed with red fluorescent dye. Nissl counterstaining is shown in green. The cell was photographed from a slice of 200 μm using a confocal laser scanning microscope. The cell body is located in the anterior border with the eminentia granularis anterior (upper right), and the axon was cut, probably projecting to the brainstem (for details see text). The dendritic tree is planar, extending for 500x700 μm in the sagittal plane, but only for 110 μm (optical thickness) medio‐laterally. Two smooth primary dendrites arise from the soma and give off secondary and tertiary branches irregularly in the molecular region. The dendrites become thinner and more spiny as they extend further from the cell body. J. Comp. Neurol. 509:1–22, 2008. © 2008 Wiley‐Liss, Inc.
Factors affecting secondary metabolite production in plants: volatile components and essential oils
Authors: Figueiredo A. Cristina , Barroso José G. , Pedro Luis G. , Scheffer Johannes J. C.
Published: May 2008

The presence, yield and composition of secondary metabolites in plants, viz. the volatile components and those occurring in essential oils, can be affected in a number of ways, from their formation in the plant to their final isolation. Several of the factors of influence have been studied, in particular for commercially important crops, to optimize the cultivation conditions and time of harvest and to obtain higher yields of high‐quality essential oils that fit market requirements. In addition to the commercial importance of the variability in yield and composition, the possible changes are also important when the essential oils and volatiles are used as chemotaxonomic tools. Knowledge of the factors that determine the chemical variability and yield for each species are thus very important. These include: (a) physiological variations; (b) environmental conditions; (c) geographic variations; (d) genetic factors and evolution; (e) political/social conditions; and also (f) amount of plant material/space and manual labour needs. Copyright © 2008 John Wiley & Sons, Ltd.
Association of Helicobacter pylori infection with chronic atrophic gastritis: Meta‐analyses according to type of disease definition
Authors: Weck Melanie N. , Brenner Hermann
Published: May 2008

Helicobacter pylori is a major risk factor for chronic atrophic gastritis (CAG). A large variety of definitions of CAG have been used in epidemiologic studies in the past. The aim of this work was to systematically review and summarize estimates of the association between H. pylori infection and CAG according to the various definitions of CAG. Articles on the association between H. pylori infection and CAG published until July 2007 were identified. Separate meta‐analyses were carried out for studies defining CAG based on gastroscopy with biopsy, serum pepsinogen I (PG I) only, the pepsinogen I/pepsinogen II ratio (PG I/PG II ratio) only, or a combination of PG I and the PG I/PG II ratio. Numbers of identified studies and summary odds ratios (OR) (95% confidence intervals) were as follows: gastroscopy with biopsy: n = 34, OR = 6.4 (4.0–10.1); PG I only: n = 13, OR = 0.9 (0.7–1.2); PG I/PG II ratio: n = 8, OR = 7.2 (3.1–16.8); combination of PG I and the PG I/PG II ratio: n = 20, OR = 5.7 (4.4–7.5). Studies with CAG definitions based on gastroscopy with biopsy or the PG I/PG II ratio (alone or in combination with PG I) yield similarly strong associations of H. pylori with CAG. The association is missed entirely in studies where CAG is defined by PG I only. © 2008 Wiley‐Liss, Inc.
Breast cancer screening: Evidence for false reassurance?
Authors: de Gelder Rianne , van As Elisabeth , Tilanus‐Linthorst Madeleine M.A. , Bartels Carina C.M. , Boer Rob , Draisma Gerrit , de Koning Harry J.
Published: May 2008

Tumour stage distribution at repeated mammography screening is, unexpectedly, often not more favourable than stage distribution at first screenings. False reassurance, i.e., delayed symptom presentation due to having participated in earlier screening rounds, might be associated with this, and unfavourably affect prognosis. To assess the role of false reassurance in mammography screening, a consecutive group of 155 breast cancer patients visiting a breast clinic in Rotterdam (The Netherlands) completed a questionnaire on screening history and self‐observed breast abnormalities. The length of time between the initial discovery of breast abnormalities and first consultation of a general practitioner (“symptom–GP period”) was compared between patients with (“screening group”) and without a previous screening history (“control group”), using Kaplan–Meier survival curves and log‐rank testing. Of the 155 patients, 84 (54%) had participated in the Dutch screening programme at least once before tumour detection; 32 (38%) of whom had noticed symptoms. They did not significantly differ from control patients (n = 42) in symptom–GP period (symptom–GP period ≥30 days: 31.2% in the symptomatic screened group, 31.0% in the control group; p = 0.9). Only 2 out of 53 patients (3.8%) with screen‐detected cancer had noticed symptoms prior to screening, reporting symptom–GP periods of 2.5 and 4 years. The median period between the first GP‐ and breast clinic visit was 7.0 days (95% C.I. 5.9–8.1) in symptomatic screened patients and 6.0 days (95% C.I. 4.0–8.0) in control patients. Our results show that false reassurance played, at most, only a minor role in breast cancer screening. © 2008 Wiley‐Liss, Inc.
Double‐filtration plasmapheresis in the treatment of leg ulcers in cryoglobulinemia
Authors: Ramunni A. , Lauletta G. , Brescia P. , Saliani M.T. , Montrone M. , Chironna M. , Sansonno D. , Dammacco F. , Coratelli P.
Published: May 2008

Hepatitis C virus (HCV) is the major cause of cryoglobulinemia. Skin lesions are frequent and can be cured from the removal of cryoglobulins by therapeutic apheresis. We describe a case of HCV‐positive type I cryoglobulinemia with severe leg ulcers, not responsive to antiviral and immunosuppressive treatment. Thirty sessions of double filtration plasmapheresis were performed, over a period of 6 months, with no other associated treatment. Before and after each session an assessment of immunoglobulins, complement, cryocrit, and fibrinogen was made. HCV RNA levels were determined in serum cryoprecipitate, supernatant before and after each session, and in the collection bag. No differences in pre and postapheresis values were observed in the serum concentrations and the supernatant, whereas the postapheresis cryoprecipitate showed a significantly reduced viral load (P< 0.02) as compared with the preapheresis values. There was improvement in the condition of ulcers in the leg during apheresis and had completely regressed by the end of the cycle. J. Clin. Apheresis, 2008. © 2008 Wiley‐Liss, Inc.
Analytical methods for calculating Continuous Symmetry Measures and the Chirality Measure
Authors: Pinsky Mark , Dryzun Chaim , Casanova David , Alemany Pere , Avnir David
Published: May 2008

We provide analytical solutions of the Continuous Symmetry Measure (CSM) equation for several symmetry point‐groups, and for the associated Continuous Chirality Measure (CCM), which are quantitative estimates of the degree of a symmetry‐point group or chirality in a structure, respectively. We do it by solving analytically the problem of finding the minimal distance between the original structure and the result obtained by operating on it all of the operations of a specific G symmetry point group. Specifically, we provide solutions for the symmetry measures of all of the improper rotations point group symmetries, Sn, including the mirror (S1, CS), inversion (S2, Ci) as well as the higher Sns (n > 2 is even) point group symmetries, for the rotational C2 point group symmetry, for the higher rotational Cn symmetries (n > 2), and finally for the Cnh symmetry point group. The chirality measure is the minimal of all Sn measures. © 2008 Wiley Periodicals, Inc. J Comput Chem 2008
The possibility of the decomposition of 2′‐deoxyribose moiety of thymidine induced by the low energy electron attachment
Authors: Liang Guoming , Bao Xiaoguang , Gu Jiande
Published: May 2008

To evaluate the possibility of the decomposition of 2‐deoxyribose moiety of thymidine induced by low energy electrons (LEE) attachment, the transition states and the energy barriers of the bond breaking processes of the ribose of the nucleoside have been studied theoretically by applying the density functional theory with the double zeta basis sets (DZP++). The energy barriers for the breakage of the CC bonds (C1′C2′, C2′C3′, C3′C4′, and C4′C5′) of the ribose group of the radical anion of thymidine are found to be high (ca. 42–57 kcal/mol). The total energies of the CC bond‐broken products are significantly higher than that of the radical anion dT•−. The decomposition of dT•− through the CC bond rupture is unlikely to take place. The rupture of the C1′O4′ bond of dT•− needs an activation energy as low as 10.4 kcal/mol. However, the reversed reaction (C1′O4′ bond formation) needs the activation energy low as 0.3 kcal/mol. Therefore, the intermediate product LM1C1′O4′ is unlikely to be stable and the C1′O4′ bond‐broken is not favored. The activation energy of the C4′O4′ bond rupture process amounts to 20.5 kcal/mol. The total energy of the C4′O4′ bond broken product is about 6.5 kcal/mol lower than that of the reactant dT•−. The subsequent N1‐glycosidic bond breaking process is found to have a very low energy barrier. Therefore, the LEE‐induced base release through the C4′O4′ bond rupture might be a possible pathway. © 2008 Wiley Periodicals, Inc. J Comput Chem 2008
The structure and chemical bonding in the N2CuX and N2···XCu (X = F, Cl, Br) systems studied by means of the molecular orbital and Quantum Chemical Topology methods
Authors: Kisowska Karolina , Berski Slawomir , Latajka Zdzislaw
Published: May 2008

Ab initiostudies carried out at the MP2(full)/6‐311+G(2df) and MP2(full)/aug‐cc‐pVTZ‐PP computational levels reveals that dinitrogen (N2) and cuprous halides (CuX, X = F, Cl, Br) form three types of systems with the side‐on and end‐on coordination of N2: NNCuX (C∞v), N2CuX (C2v) stabilized by the donor–acceptor bonds and weak van der Waals complexes N2···XCu (C2v) with dominant dispersive forces. An electron density transfer between the N2and CuX depends on type of the N2coordination and a comparison of the NPA charges yields the [NN]δ+‐[CuX]δ−and [N2]δ−‐[CuX]δ+formula. According to the NBO analysis, the CuN coordinate bonds are governed by predominant LPN2→σ*(CuX) “2e‐delocalization” in the most stable NNCuX systems, meanwhile back donation LPCu→π*(NN) prevails in less stable N2CuX molecules. A topological analysis of the electron density (AIM) presents single BCP between the Cu and N nuclei in the NNCuX, two BCPs corresponding to two donor‐acceptor CuN bonds in the N2CuX and single BCP between electron density maximum of the NN bond and halogen nucleus in the van der Waals complexes N2···XCu. In all systems values of the Laplacian ∇2ρ(r)(rBCP) are positive and they decrease following a trend of the complex stability i.e. NNCuX (C∞v) > N2CuX (C2v) > N2···XCu (C2v). A topological analysis of the electron localization function (ELF) reveals strongly ionic bond in isolated CuF and a contribution of covalent character in the CuCl and CuBr bonds. The donor–acceptor bonds CuN are characterized by bonding disynaptic basins V(Cu,N) with attractors localized at positions corresponding to slightly distorted lone pairs V(N) in isolated N2. In the NNCuX systems, there were no creation of any new bonding attractors in regions where classically the donor–acceptor bonds are expected and there is no sign of typical covalent bond CuN with the bonding pair. Calculations carried out for the NNCuX reveal small polarization of the electron density in the NN bond, which is reflected by the bond polarity index being in range of 0.14 (F) to 0.11 (Cl). © 2008 Wiley Periodicals, Inc. J Comput Chem 2008
Circular dichroism enhancement in large DNA aggregates simulated by a generalized oscillator model
Authors: Andrushchenko Valery , Bouř Petr
Published: May 2008

An increased circular dichroism (CD) signal of large molecular aggregates formed upon DNA condensation was observed a long time ago, and is often referred to as ψ‐CD. The effort to understand this phenomenon is further motivated by the latest DNA packing studies and advances in macromolecular chemistry. In the present work, the transition dipole coupling model describing interactions of molecules with light has been extended to handle systems of arbitrary size. The analytical formulae obtained retain the simplicity and computational speed of the standard approach. The origin of the ψ‐effect was investigated on several model systems. The results suggest that the CD enhancement is primarily caused by delocalized phonon‐like excitations in nucleic acid strands. The size of the system exhibiting the effect thus does not need to be comparable with or greater than the wavelength of the absorbed light. Small structural irregularities still allow for the enhancement while a larger disorder breaks it. The modeling is consistent with previous experimental electronic and vibrational CD studies, and makes it possible to correlate the enhancement with the geometry of the nucleic acid systems. © 2008 Wiley Periodicals, Inc. J Comput Chem 2008