bluuebunny/crossref_metadata_2025_split huggingface dataset:
Free Fatty Acids Induce a Proinflammatory Response in Islets via the Abundantly Expressed Interleukin-1 Receptor I
Authors: Böni-Schnetzler Marianne , Boller Simone , Debray Sarah , Bouzakri Karim , Meier Daniel T. , Prazak Richard , Kerr-Conte Julie , Pattou Francois , Ehses Jan A. , Schuit Frans C. , Donath Marc Y. 
Published: October 2009

AbstractIslets of patients with type 2 diabetes mellitus (T2DM) display features of an inflammatory process including elevated levels of the cytokine IL-1β, various chemokines, and macrophages. IL-1β is a master regulator of inflammation, and IL-1 receptor type I (IL-1RI) blockage improves glycemia and insulin secretion in humans with T2DM and in high-fat-fed mice pointing to a pivotal role of IL-1RI activity in intra-islet inflammation. Given the association of dyslipidemia and T2DM, we tested whether free fatty acids (FFA) promote the expression of proinflammatory factors in human and mouse islets and investigated a role for the IL-1RI in this response. A comparison of 22 mouse tissues revealed the highest IL-1RI expression levels in islets and MIN6 β-cells. FFA induced IL-1β, IL-6, and IL-8 in human islets and IL-1β and KC in mouse islets. Elevated glucose concentrations enhanced FFA-induced proinflammatory factors in human islets. Blocking the IL-1RI with the IL-1R antagonist (IL-1Ra) strongly inhibited FFA-mediated expression of proinflammatory factors in human and mouse islets. Antibody inhibition of IL-1β revealed that FFA stimulated IL-1RI activity via the induction of the receptor ligand. FFA-induced IL-1β and KC expression in mouse islets was completely dependent on the IL-1R/Toll-like receptor (TLR) docking protein Myd88 and partly dependent on TLR2 and -4. Activation of TLR2 in purified human β-cells and islets stimulated the expression of proinflammatory factors, and IL-1RI activity increased the TLR2 response in human islets. We conclude that FFA and TLR stimulation induce proinflammatory factors in islets and that IL-1RI engagement results in signal amplification.
Impact of Simvastatin on Adipose Tissue: Pleiotropic Effects in Vivo
Authors: Khan Tayeba , Hamilton Mark P. , Mundy Dorothy I. , Chua Streamson C. , Scherer Philipp E. 
Published: October 2009

AbstractStatins belong to a class of drugs well known for their ability to reduce circulating low-density lipoprotein cholesterol. In addition to cholesterol lowering, they also exhibit potential antiinflammatory and antioxidant properties, suggesting that tissues other than liver may be targeted by statins to exert their beneficial metabolic effects. Adipocytes have received very little attention as a potential target of these drugs, possibly because adipocytes are not a major source of biosynthetic cholesterol. Here, we examine the effects of simvastatin on the secretory pathway, inflammation, and cellular metabolism of adipocytes as well as on whole-body insulin sensitivity. We find that statins have a selective effect on the secretion of the insulin-sensitizing adipokine adiponectin by reducing circulating levels of the high-molecular-weight form of adiponectin specifically with a concomitant increase in intracellular adiponectin levels. However, these effects on adiponectin do not translate into changes in metabolism or whole-body insulin sensitivity, potentially due to additional antiinflammatory properties of statins. In addition, ob/ob mice treated with statins have reduced adiposity and an altered ultrastructure of the plasma membrane with respect to caveolar histology. Our data demonstrate that statins have major effects on the cellular physiology of the adipocyte on multiple levels.
Smad1-Smad5 Ovarian Conditional Knockout Mice Develop a Disease Profile Similar to the Juvenile Form of Human Granulosa Cell Tumors
Authors: Middlebrook Brooke S. , Eldin Karen , Li Xiaohui , Shivasankaran Sujatha , Pangas Stephanie A. 
Published: October 2009

AbstractGranulosa cell tumors (GCTs) of the ovary are rare sex cord stromal tumors. Although generally indolent, GCTs recur, and if not diagnosed and treated in early stages, survival rates are significantly shortened. Very little is known regarding GCT etiology. Because of the low incidence of cases and lack of standard diagnostics, mouse models for granulosa cell tumors are a valuable tool for studying GCTs and provide models for developing diagnostic and treatment strategies. We recently developed a novel mouse model of metastatic granulosa cell tumors by genetic deletion of the bone morphogenetic protein signaling transcription factors (SMADs) in granulosa cells of the ovary. Histological and serum hormone analyses reveal that this mouse model most closely resembles the juvenile form of GCT. We further analyzed samples of human juvenile GCT (JGCT) for expression of anti-Müllerian hormone and activation of two major signaling pathways: TGFβ/SMAD2/3 and wingless-related mouse mammary tumor virus integration site (Wnt)/β-catenin. The TGFβ family is active in mouse Smad1-Smad5 double knockout tumors, and here we show that this pathway, but not the β-catenin pathway, is activated in samples of human JGCT. These data suggest that the SMAD family, possibly through disruption of SMAD1/5 or activation of SMAD2/3 may contribute to the pathogenesis of JGCT in humans.
Phosphodiesterase 8B Gene Polymorphism Is Associated with Subclinical Hypothyroidism in Pregnancy
Authors: Shields Beverley M. , Freathy Rachel M. , Knight Bridget A. , Hill Anita , Weedon Michael N. , Frayling Timothy M. , Hattersley Andrew T. , Vaidya Bijay 
Published: October 2009

Background: Maternal subclinical hypothyroidism is associated with a number of adverse outcomes in pregnancy. The Endocrine Society’s recent consensus guidelines have recommended treatment with T4 for this condition in pregnancy. The single nucleotide polymorphism rs4704397 in the phosphodiesterase 8B (PDE8B) gene has been found to be associated with altered serum TSH concentrations in the general population. We aimed to assess whether genetic variation in TSH due to the rs4704397 genotype affects the number of individuals classified as having subclinical hypothyroidism in pregnancy.
Methods: Serum TSH, FT4, FT3, and thyroid peroxidase antibodies (TPOAbs) were measured in 970 pregnant women at 28 wk gestation. rs4704397 genotype was available on 877 subjects. Reference range calculations were based on the TPOAb-negative women.
Results: TSH, but not FT4, FT3, or TPOAbs, varied with genotype and was highest in those with the AA genotype (median, 2.16, 1.84, and 1.73 mIU/liter for AA, AG, and GG genotypes, respectively; P = 0.0004). A greater proportion of women with the AA genotype had TSH concentrations above 4.21 mIU/liter, the upper limit of the reference range, compared with the AG and GG genotypes (9.6 vs. 3.5%, respectively; P = 0.004). Maternal PDE8B genotype was not associated with offspring birthweight or gestational age at delivery.
Conclusion: Genetic variation in TSH levels in pregnancy associated with the PDE8B rs4704397 genotype has implications for the number of women treated for subclinical hypothyroidism under current guidelines. Consideration should be made to individualization of normal ranges, potential effects on pregnancy outcome, and intention to treat for subclinical hypothyroidism in pregnancy.
Variation in the PDE8B gene leads to alteration in serum TSH concentration and different proportions of women picked up with subclinical hypothyroidism in pregnancy.
Trans-Vacant and cis-Vacant 2:1 Layer Silicates: Structural Features, Identification, and Occurrence
Authors: Drits Victor A. , Zviagina Bella B. 
Published: October 2009

AbstractA comprehensive study of clay minerals should include determination of the vacancy pattern of the dioctahedral sheet. The purpose of this report is to consider the advantages and limitations in various diffraction and non-diffraction methods for the determination of the layer types in clay minerals. Identification of trans-vacant (tv) and cis-vacant (cv) clay minerals reported here is based on powder X-ray diffraction (XRD) patterns calculated for different polytypes consisting of either tv or cv layers, on the simulation of experimental XRD patterns corresponding to illite or illite fundamental particles in which tv and cv layers are interstratified, and on the semi-quantitative assessment of the relative content of the layer types in the interstratified structures by generalized Méring’s rules. A simple and effective method for identification of tv and cv layers in dioctahedral 2:1 layer silicates employs thermal analysis and is based on different dehydroxylation temperatures for tv and cv illite and smectite layers.Crystal chemical analysis of various dioctahedral 2:1 layer silicates consisting of tv and cv layers indicates that compositional control is present in the distribution of octahedral cations over trans- and cis-sites. In dioctahedral smectites the formation of tv and cv layers is related to the layer composition and local order-disorder in the distribution of isomorphous cations. Dioctahedral 1M micas with abundant Fe3+ and Mg occur only as tv varieties. In contrast, 1M-cv illite, as well as cv layers in illite fundamental particles of I-S, can form only as Fe- and Mg-poor varieties. In illites and illite fundamental particles of I-S consisting of tv and cv layers, cv layers prevail when the amounts of Al in octahedra and tetrahedra are >1.55 and >0.35 atoms per O10(OH)2, respectively.The main factors responsible for the stability of cv and tv illites have been established. Monomineral cv 1M illite, its association with tv 1M illite, and interstratified cv/tv illite occur around ore deposits, in bentonites, and in sandstones mostly as a result of different types of hydrothermal activity. The initial material for their formation should be Al-rich, and hydrothermal fluids should be Mg- and Fe-poor.Tv and cv smectites of volcanic origin differ in terms of octahedral cation composition and distribution of isomorphous octahedral cations. Mg-rich cv smectites have random distribution of isomorphous octahedral cations, whereas in Mg-bearing tv smectites octahedral Mg cations are dispersed so as to minimize the amount of Mg-OH-Mg arrangements.
Mineralogical Composition of Shallow Soils on Basic and Ultrabasic Rocks of East Fennoscandia and of the Ural Mountains, Russia
Authors: Lessovaia S. N. , Polekhovsky Yu. S. 
Published: October 2009

AbstractThe influence of epigenetic (pre-pedogenetic) alteration of basic and ultrabasic rocks leading to the formation of phyllosilicate mineral associations is not well known. The purpose of this study was to gain further understanding of the processes involved by investigating the mineral associations of shallow soils underlain by amphibolites and metamorphosed gabbro-diabases (East Fennoscandia) and by serpentinous dunites (olivinite) and metagabbro amphibolites (the Ural Mountains). Where phyllosilicates were absent from the bedrock, they were also absent from the sola. The pedogenic alteration of the initial mineral soil matrix was very weak and did not result in a significant accumulation of phyllosilicates in the soils (East Fennoscandia). Pedogenesis enhanced the transformation of phyllosilicates, a process initiated by epigenic rock alteration.Phyllosilicates in the sola from basic and ultrabasic rocks of the Polar Urals were largely inherited according to their origin. The inherited phyllosilicate association of the sola from ultrabasic rocks included talc, serpentine, and chlorite. Saponite resulted from pedogenesis; its distribution in various thin soils depending on the processes of neoformation and decomposition, the latter probably taking place under the influence of lichens and moss.Chlorite and illite and products of their transformation, including vermiculite, comprise the phyllosilicate association of a solum from basic rock, and traces of talc were found. The distribution of vermiculite and randomly interstratified chlorite-vermiculite (C-V) depended on the processes of chlorite vermiculitization and vermiculite decomposition.
Cation Exchange Reactions of Vermiculite With Cu-Triethylenetetramine as Affected by Mechanical and Chemical Pretreatment
Authors: Steudel Annett , Weidler Peter G. , Schuhmann Rainer , Emmerich Katja 
Published: October 2009

AbstractThe cation exchange capacity (CEC) is a characteristic property of expandable clay minerals, such as smectites and vermiculites. The aim of this work was to examine the cation exchange behavior of vermiculite using the Cu-triethylenetetramine (Cu-trien) CEC method and the influence of mechanical and chemical pretreatment, with the ammonium acetate method serving as a reference. The Cu-trien method makes rapid and direct CEC measurements possible. Three different kinds of mill were used to grind a vermiculite sample from Russia, in order to reduce the particle size to <10 µm. The Netzsch CGS 10 dry mill reduced the particle size more effectively than the other grinding methods. Chemical pretreatments were used to remove carbonates, organic matter, Fe oxides, and divalent exchangeable cations from vermiculite samples prior to CEC measurements. Subsamples of ground and chemically pretreated vermiculite samples were saturated with Na, Li, Mg, Ca, and Cu cations to determine the effect of exchangeable cations on measured CEC values. Chemical pretreatment, monovalent cation pretreatment, and 48 h of shaking time were needed to measure vermiculite CEC values effectively using the Cu-trien method.
Array-Based Comparative Genomic Hybridization Application for Revealing Genomic Micro Imbalances in Congenital Malformations
Authors: Hadjidekova S , Toncheva D 
Published: October 2009

Array-Based Comparative Genomic Hybridization Application for Revealing Genomic Micro Imbalances in Congenital MalformationsBirth defects affect 3-5% of live births and are a major cause of fetal, neonatal and infant morbidity and mortality in all industrialized countries. Some 40-60% of congenital physical anomalies in humans have no cause, 20% that seem to be multifactorial, 10-13% environmental and 12-25% genetic.Classical cytogenetic or common comparative genomic hybridization (CGH) methods have limited use in investigation of the whole genome because of their low resolution (5-10 Mb). Fluorescencein situhybridization (FISH) and quantitative fluorescence polymerase chain reaction (QF-PCR) have higher resolution but do not allow genome-wide screening and require some prior knowledge regarding the suspected chromosomal abnormality and its genomic location.Because of these limitations, the impact of genetic micro imbalances as etiological factors for the development of congenital malformations (CM) is underestimated. Array-based techniques have enabled higher resolution screens for genomic imbalances in CM as they permit identification of micro aberrations with a size between 60 bp and several hundred kilobases. They make possible screening of the whole genome and detection of novel unbalanced micro structural rearrangements in a single reaction and also effective screening of new dose-dependent genes. In addition, the application of the aCGH technology has the potential to improve our understanding of the normal quantitative variants of the human genome.
Web-Based Software for Storage, Statistical Processing and Analysis of SNP Data in Studies on Complex Disorders
Authors: Betcheva E , Betchev C , Toncheva D 
Published: October 2009

Web-Based Software for Storage, Statistical Processing and Analysis of SNP Data in Studies on Complex DisordersSingle nucleotide polymorphisms (SNPs) have become a very powerful tool for molecular genetics studies. Public databases provide information on over 10 million polymorphisms in the human genome. The candidate gene approach and genomewide association studies through SNP analysis have opened a new avenue for defining the genetics of complex disorders. However, analysis of large numbers of SNPs is time-consuming, cost-intensive, and requires huge experimental and statistical resources in association studies. We have developed a web-based product that facilitates the processing and statistical analysis of SNP-genotyping data for casecontrol association studies and provides for custom design, a structured database and practical export layout. Here we describe the software product database and how it helps in high-speed comprehensive SNP analysis.
Polymorphism of Biotransformation Genes and Risk of Relapse in Childhood Acute Leukemia
Authors: Gra O , Kozhekbaeva Zh , Makarova O , Samochatova E , Nasedkina T 
Published: October 2009

Polymorphism of Biotransformation Genes and Risk of Relapse in Childhood Acute LeukemiaLeukemia is a hematological malignancy that involves bone marrow. Polymorphism of biotransformation genes plays an important role in primary childhood leukemia and affects the incidence and character of acute leukemia relapse. A biochip designed to assess some polymorphisms of biotransformation genes was used to determine the frequency of the polymorphic variants ofCYP1A1, CYP2D6, GSTT1, GSTM1, MTHFR, MTRR, NQO1, CYP2C9, CYP2C19andNAT2in 332 children with acute lymphoblastic leukemia (ALL) and 71 children with acute myeloblastic leukemia (AML). TheCYP1A1 *1/*2A, GSTT1non null andGSTM1non null genotypes were more frequent in patients with primary leukemia than in relapse. Analysis of theNAT2genotype frequency revealed a characteristic genotype for each type of leukemia, which prevailed in patients with relapse: the genotype341C/-, 481T/-, 590G/G, 857G/Gprevailed in ALL patients with relapse, and the genotype341T/T, 481C/C, 590A/- in AML patients with relapse when compared with patients having primary ALL or AML, respectively. Thus, the polymorphisms ofCYP1A1, GSTT1, GSTM1andNAT2genes can be considered as markers for risk of relapse in childhood acute leukemia and can be used for the prognosis and individualization of standard therapy.
Five Novel Mutations in Cystinuria Genes SLC3A1 and SLC7A9
Authors: Popovska-Jankovic K , Tasic V , Bogdanovic R , Miljkovic P , Baskin E , Efremov G , Plaseska-Karanfilska D 
Published: October 2009

Five Novel Mutations in Cystinuria Genes SLC3A1 and SLC7A9Cystinuria is an autosomal recessive disorder that is characterized by impaired transport of cystine, lysine, ornithine and arginine in the proximal renal tubule and epithelial cells of the gastrointestinal tract. The transport of these amino acids is mediated by the rBAT/b0,+AT transporter, the subunits of which are encoded by the genes SLC3A1, located on chromosome 2p16.3-21, and SLC7A9, located on chromosome 19q12-13.1. Based on the urinary cystine excretion patterns of obligate heterozygotes, cystinuria is classified into type I (normal amino acid urinary pattern in heterozygotes) and non type I (a variable degree of urinary hyper excretion of cystine and dibasic amino acids in heterozygotes). On the basis of genetic aspects, cystinuria is classified into type A, is caused by mutations in both alleles of SLC3A1; type B, caused by mutations in both alleles of SLC7A9 and type AB, is caused by one mutation in SLC3A1 and one mutation in SLC7A9. Here we present two novel mutations in the SLC3A1 gene (C242R and L573X), which were found in patients from Serbia, and three in the SLC7A9 gene (G73R, V375I, 1048-1051 delACTC), found in patients from Serbia, Macedonia and Turkey, respectively.
The evolution of government policy towards English higher education 1979-2007
Authors: Welch Penny 
Published: October 2009

Using statistics, documentary evidence and commentary from academics and academic trades unions, this article analysesthe key features of U.K. government policy towards highereducation in England since 1979. The focus is on Englandbecause the details of policy and policy implementation varybetween the four nations of the U.K. My findings support the view that, over the whole period, successive governments established increasing central control over the higher education system and mobilised it to meet goals compatible with government interpretations of the national interest. In the process, the total number ofstudents in U.K. higher education has trebled, the average cost of astudent place has almost halved and the proportion of income frompublic funds has fallen to 55% (Universities UK 2007).
Low‐Distortion Holographic Data Storage Media Using Free‐Radical Ring‐Opening Polymerization
Authors: Choi Kyongsik , Chon James W. M. , Gu Min , Malic Nino , Evans Richard A. 
Published: October 2009

AbstractHolographic data storage, due to its potential to increase capacity beyond one terabyte per disk, is tipped to be one of the next generation optical data storage technologies. Polymer‐based systems are leading candidates due to their high dynamic range, high sensitivities, and flexible and easy production, and yet polymerization‐shrinkage‐induced distortion is a major hurdle for its reliable use. In this paper, a new free radical polymerization holographic recording medium, based on low shrink cyclic allylic sulfides (LS‐CASs) ring‐opening monomers, is proposed and demonstrated. The percentage of volume shrinkage is measured to be 0.02%, with refractive index (RI) contrast of (1.01 ± 0.5) × 10−3. The measured volume shrinkage is, to the authors' best knowledge, the best reported so far in the literature. Other parameters such as sensitivity, dynamic range, and dark reaction properties are also measured, where the values can be optimized with high RI functional groups without sacrificing the low shrinkage.
Integrated Multifunctional Nanosystems for Medical Diagnosis and Treatment
Authors: Shi Donglu 
Published: October 2009

AbstractThis article provides an overview on the development of integrated multifunctional nanosystems for medical diagnosis and treatment. In particular, a novel system is developed specifically for achieving simultaneous diagnosis and treatment of cancer. Critical issues are addressed on the architecture and assembly of nanocomponents based on medical requirements: targeted in vivo imaging, controlled drug release, localized hyperthermia, and toxicity. Nanotube‐based carriers are summarized with surface functionalized properties. Other types of nanocarriers are also included such as super paramagnetic composite nanospheres and biodegradable hydroxylapatite nanoparticles. In addition, polymeric‐based nanosystems are introduced with several novel features: they can be bio‐dissolved due to environmental pH and temperature fluctuations. The nanocarriers are surface tailored with key functionalities: surface antibodies for cell targeting, anti‐cancer drug loading, and magnetic nanoparticles for both hyperthermia and MRI. Future requirements, aims, and trends in the development of multifunctional nanosystems, particularly with intelligent functionalities for fundamental studies, are also provided.