bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

AbstractSarco(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

Abstract

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

AbstractAnimals 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

AbstractNitric 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

Abstract
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

AbstractThe 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

AbstractOne 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

AbstractHow 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

AbstractIn 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

AbstractThe 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

AbstractIn 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

AbstractWe 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

AbstractMorphological 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

AbstractThe 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

AbstractPortal 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

AbstractThe 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

AbstractNonalcoholic 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.