bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mapping of conformational autoantibody epitopes in ZNT8
Authors: Wenzlau Janet M. , Frisch Lisa M. , Hutton John C. , Davidson Howard W. 
Published: November 2011

AbstractBackgroundIdentification of the major humoral epitopes in zinc transporter 8 (ZnT8) will expand the range of biomarkers for human type 1 diabetes and may provide clues to the mechanisms governing disease progression. Our initial studies suggested that most ZnT8‐reactive sera recognize conformational epitopes in the final 100aa region of the molecule. Subsequently we identified residue 325 as a major determinant in two epitopes linked to a genetic polymorphism with high minor allele frequency (rs13266634). The goal of the current study was to extend this analysis to identify non‐polymorphic epitopes in ZnT8.MethodsAlthough the carboxy‐terminal domains of human and mouse ZnT8 are ∼80% identical, the mouse probe is not precipitated by the majority of human type 1 diabetes sera. Thus to identify key residues we systematically ‘humanized’ the mouse probe at each position that differs and evaluated the probes in radio‐immunoassays.ResultsAs previously reported, only the alteration of Q > R325 by itself showed any restoration of binding to human sera. However, when clusters of structurally adjacent variant residues were also changed an additional region of antigenicity was revealed that depended on residues R332, E333, K336, and K340. Using a panel of 112 sera from recent onset subjects tested with the hC325Q and m‐R325R332E333K336K340 probes, 39.3% of the subjects were ZnT8(Q)A+, of which 38.6% (17/44) also recognized the mouse probe.ConclusionsWe conclude that the mR‐REKK probe identifies a third major epitope in ZnT8 that may add to the diagnostic utility of measuring autoantibodies to this molecule. Copyright © 2011 John Wiley & Sons, Ltd.
Development of a novel autoantibody assay for autoimmune gastritis in type 1 diabetic individuals
Authors: Wenzlau J. M. , Gardner T. J. , Frisch L. M. , Davidson H. W. , Hutton J. C. 
Published: November 2011

AbstractBackgroundAutoimmune atrophic body gastritis (ABG) and pernicious anaemia are prototypical, organ‐specific autoimmune diseases whose prevalence in the general population is 2.0 vs 2 and 0.15–1%, respectively. The incidence of disease increases with age and is frequently associated with other autoimmune disorders such as type 1 diabetes mellitus (T1DM). Early diagnosis of ABG/pernicious anaemia is essential for the prevention and/or treatment before manifestations of chronic disease become irreversible. Parietal cell autoantibody detection via enzyme‐linked immunosorbent assay is currently the most widely used biomarker of disease with diagnosis confirmed by subsequent immunohistochemistry via biopsy.MethodsTo improve the assay we designed a specific, molecularly defined radioimmunoprecipitation assay for early detection of ABG, targeting its major antigen, the gastric H+/K+ ATPase 4A subunit ATP4A.ResultsThe major antigenic domain in ATP4A was tested against a panel of sera from new onset patients with T1DM which tested positive for the gold standard T1DM autoantibodies (IAA, IA2A, GAD65A, and ZnT8A). Significant immunoreactivity to ATP4A was measured (25%) while 6% of first‐degree relatives of subjects with T1DM who were sero‐negative for T1DM autoantigens were positive for ATP4A autoantibodies. ATP4A antibody prevalence increased with age of onset of T1DM, which is atypical of other T1DM autoantibodies. Immunoreactivity to ATP4A, unlike that of T1DM antigens, demonstrates a significant gender bias in newly diagnosed individuals with T1DM.ConclusionAlthough the utility of the assay as a biomarker for T1DM is likely limited, it may serve as an improved indicator of ABG. Copyright © 2011 John Wiley & Sons, Ltd.
LIPS islet autoantibody assays in high‐throughput format for DASP 2010
Authors: Marcus Patrick , Yan Xiang , Bartley Bryan , Hagopian William 
Published: November 2011

AbstractBackgroundFor cost‐effective population‐based diabetes prediction and confirmation, islet autoantibody assays must be made more economical.MethodsWe evaluated glutamic acid decarboxylase (GAD)‐Ruc (renilla luciferase) and IA2ic (also known as ICA512ic)‐Ruc (renilla luciferase) fusion protein constructs in high‐throughput islet antibody assay formats.ResultsAntigen production via transfection onto COS cells in 100 mm culture dishes yielded sufficient antigen to assay 375 and 535 serum samples for GAD and IA2ic per dish, respectively. Antigen was usably stable after − 80 °C storage for 40–80 days after which luciferase activity decreased. The mean signal‐to‐noise ratios for luciferase‐based immunoprecitation system (LIPS) GAD and LIPS IA2ic were 88 ± 24 and 219 ± 89, respectively, comparing favourably to radio‐binding assays (RBA) in the same format. However, the coefficient of variation among triplicate wells was higher for IA2ic than for GAD in LIPS, similar to findings in RBA format. Correlation coefficients between autoantibody indices determined from the RBA and LIPS methods were only R2 = 0.79 and R2 = 0.75 for GAD and IA2ic, respectively, raising the possibility that different epitopes were favoured in the two different assay formats. Nevertheless, overall concordance for the two assay types was high, at 228/240 = 95.0% for GAD and 494/521 = 94.8% for IA2ic. Using optimal cutoffs, Diabetes Autoantibody Standardization Program (DASP) 2010 sensitivity/specificity was 80/99% for GAD RBA, 80/99% for GAD LIPS, 70/98% for IA2 RBA, and 72/99% for IA2 LIPS.ConclusionThe LIPS assays for islet autoantibodies to GAD and IA2ic performed as well as RBA in DASP 2010. With further refinements in expression and storage, these assays may be more economical than current methods to measure islet autoantibodies in type 1 diabetes. Copyright © 2011 John Wiley & Sons, Ltd.
Zinc transporter 8 autoantibodies in fulminant, acute‐onset, and slow‐onset patients with type 1 diabetes
Authors: Kawasaki Eiji , Nakamura Kan , Kuriya Genpei , Satoh Tsuyoshi , Kobayashi Masakazu , Kuwahara Hironaga , Abiru Norio , Yamasaki Hironori , Matsuura Nobuo , Miura Junnosuke , Uchigata Yasuko , Eguchi Katsumi 
Published: November 2011

AbstractBackgroundThe aim of this study was to determine the prevalence and role of autoantibodies to zinc transporter 8 (ZnT8A) in three forms (fulminant, acute‐onset, and slow‐onset) of Japanese patients with type 1 diabetes.MethodsOne‐hundred and ninety‐six new‐onset patients with type 1 diabetes were studied: 85 were fulminant, 81 acute‐onset, and 30 slow‐onset type 1 diabetes. ZnT8A were determined by radioimmunoassay using a hybrid ZnT8 carboxy‐terminal construct (aa268‐369) carrying 325Trp and 325Arg. Furthermore, ZnT8A epitopes were analysed using ZnT8 constructs incorporating the known aa325 variants (Trp, Arg, and Gln).ResultsZnT8A were detected in 58% patients with acute‐onset and 20% with slow‐onset type 1 diabetes (p < 0.0005). In contrast, none of sera from fulminant type 1 diabetes were reactive to ZnT8 construct. Conversion of Arg or Trp to Gln at aa325 abolished reactivity in 59% of patients with an age of onset > 10 years, which was significantly higher than that in patients ⩽10 years of age (33%, p < 0.05).ConclusionsThese results suggest that ZnT8A are an additional useful marker for acute‐onset type 1 diabetes, but not a diagnostic marker for fulminant type 1 diabetes, and ZnT8A epitope recognition is different according to the onset age. Copyright © 2011 John Wiley & Sons, Ltd.
Mast cell stabilization: novel medication for obesity and diabetes
Authors: Wang Jing , Shi Guo‐Ping 
Published: November 2011

AbstractMast cells are essential in allergic responses and beyond. White adipose tissue from obese humans contains large numbers of mast cells. Serum mast cell tryptase levels are also significantly higher in obese subjects than in lean subjects, suggesting a role of these inflammatory cells in obesity and diabetes. Two types of mast cell‐deficient mice, along with corresponding wild‐type control mice, were fed a Western diet to induce obesity and diabetes. We also used two anti‐allergy drugs, cromolyn and ketotifen (Zaditor), to treat wild‐type mice during intake of a Western diet or after the onset of obesity and diabetes, to examine the possible prevention or reversal of these conditions. Mast cell deficiency or pharmacological stabilization reduced body weight gain and improved glucose and insulin sensitivities. These common, side effect‐free drugs also reduced pre‐established obesity and diabetes without noticeable toxicity. Mechanistic studies suggest that mast cells participate in these metabolic disorders by affecting energy expenditure, protease expression, angiogenesis, apoptosis, and preadipocyte differentiation. These observations open a new era of basic research regarding mast cells, and offer hope to patients suffering from these metabolic disorders. Copyright © 2011 John Wiley & Sons, Ltd.
‘Sensing’ the link between type 1 and type 2 diabetes
Authors: Tsui Hubert , Paltser Geoffrey , Chan Yin , Dorfman Ruslan , Dosch H. Michael 
Published: November 2011

AbstractObesity‐associated insulin resistance is a core element of metabolic syndrome and type 2 diabetes (T2D). Notably, insulin resistance is also a feature of type 1 diabetes (T1D), where findings in the non‐obese diabetic mouse model have implicated transient receptor potential vanilloid‐1 (TRPV1+) sensory neurons in local islet inflammation and glucose metabolism. Here, we briefly review the role of TRPV1 in non‐obese diabetic (NOD) T1D pathogenesis, highlighting commonalities that suggest TRPV1 may contribute to obesity and T2D as well. With the recently discovered importance of adipose infiltrating lymphocytes in the metabolic disturbances of obesity and T2D, sensory innervation of fat may thus play an analogous role to sensory neurons in the islet—modulating neuroendocrine homeostasis and inflammation. In such a scenario, TRPV1+ sensory nerves would provide the pathoaetiological link connecting the shared metabolic and immunologic features of type 1 diabetes and T2D. Copyright © 2011 John Wiley & Sons, Ltd.
Prevention of type 1 diabetes by inducing subclinical dermatitis on a small area
Authors: Engkilde Kaare , Johansen Jeanne Duus , Hansen Axel Kornerup , Menné Torkil , Buschard Karsten 
Published: November 2011

AbstractObjectiveWe have previously epidemiologically shown that type 1 diabetes is inversely associated with contact allergy. This finding is intriguing as type 1 diabetes and contact allergy are two completely different diseases, although T cells are involved in both diseases. The objective of this study was therefore to experimentally study the effect of contact allergens on the development of diabetes in non‐obese diabetic mice.MethodsNon‐obese diabetic mice 4 weeks of age were separated into seven groups. One group was exposed to tapped water every 14th day, whereas the remaining six groups were split into sensitizations groups or elicitation groups (exposure every 14th day). These groups were then treated with one of the selected contact allergens (PPD or DNCB) or vehicle (AOO). All groups received the sensitizing treatment regime, and hereafter only the elicitation groups were further treated. If the blood glucose reached 14 mM, the mice were considered diabetic and euthanized. Cardiac heart blood was drawn at euthanization, and a Luminex analysis was done on the serum.ResultsWe showed that repeated application of a low dose of PPD reduced the incidence of diabetes compared to application with water (47% versus 93%, p = 0.004). The rest of the groups developed diabetes with a cumulative incidence rate above 80%. The Luminex cytokine analysis revealed no differences between the groups, and no elevated cytokine level suggested a systemic response. Dermatitis was not noticeable by visual inspection, a histological examination, however, revealed a slight infiltration in the ears in the elicitation groups exposed to contact allergens.ConclusionThis study showed that repeated topical application on the ears with a contact allergen could prevent the development of diabetes in non‐obese diabetic mice. The contact allergens gave a non‐visible, subclinical dermatitis on the application site. Activation of NKT cells to the ear lymph nodes seems to be involved. Copyright © 2011 John Wiley & Sons, Ltd.
Two promoters with distinct activities in different tissues drive the expression of heparanase in Xenopus
Authors: Bertolesi Gabriel E. , Su Hsiao Yuan , Michaiel George , Dueck Stephanie M. , Hehr Carrie L. , McFarlane Sarah 
Published: November 2011

AbstractIn Xenopus laevis embryos, heparanase, the enzyme that degrades heparan sulfate, is synthesized as a preproheparanase (XHpaL) and processed to become enzymatically active (XHpa active). A short nonenzymatic heparanase splice variant (XHpaS) is also expressed. Using immunohistochemistry, Western blot, and heparanase promoter analysis, we studied the dynamic developmental expression of the three heparanases. Our results indicate that (1) all three isoforms are maternally expressed; (2) XHpaS is a developmental variant; (3) in the early embryo, heparanase is localized to both the plasma membrane and the nucleus; (4) several tissues express heparanase, but expression in the developing nervous system is most evident; (5) two promoters with distinct activities in different tissues drive heparanase expression; (6) Oct binding transcription factors may modulate heparanase promoter activity in the early embryo. These data argue that heparanase is expressed widely during development, but localization and levels are finely regulated. Developmental Dynamics 240:2657–2672, 2011. © 2011 Wiley Periodicals, Inc.
Lipid oxidation inhibiting capacities of blackseed essential oil and rosemary extract
Authors: Erkan Naciye , Ayranci Guler , Ayranci Erol 
Published: November 2011

AbstractLipid oxidation is the main deterioration process that occurs in vegetable oils containing lipid molecules with polyunsaturation. The aim of the present study was to investigate the possible effects of blackseed (Nigella sativa L.) essential oil (BEO) and rosemary (Rosmarinus officinalis L.) extract (RE) on stabilization of sunflower oil under accelerated storage conditions. RE was obtained by soxhlet extraction using methanol, whereas BEO was hydrodistilled from the blackseed extract obtained by extraction using petroleum ether (b.p. 40–60°C). The results indicate that both extracts stabilize sunflower oil to a certain extent, the extent being greater with RE than with BEO based on measurements of peroxide value, p‐anisidine value, amount of nonoxidized linoleic acid in saponified oil samples by HPLC‐DAD, concentration of conjugated diene hydroperoxide, and UV light absorption. The oil stabilizing effect of BEO against lipid oxidation, especially at concentrations of 0.06 and 0.1 g/100 g oil was found to increase as the temperature increased, according to principal component analysis results. Based on its strong lipid oxidation inhibiting capacity, RE can be used as a potential natural extract for stabilizing sunflower oil against oxidation. BEO, at carefully selected concentrations, can be suggested as an alternative supplement of plant origin for improving oil stabilization.Practical applications: Sunflower oil is a widely used vegetable oil for cooking and frying, and has a high linoleic acid content of about 40–70%. Here we show that sunflower oil can be stabilized by adding rosemary and blackseed extracts. The treatment can be useful especially in applications which require heating the oil to high temperatures.
Generalized linear model describes determinants of total antioxidant capacity of refined vegetable oils
Authors: Castelo‐Branco Vanessa Naciuk , Torres Alexandre Guedes 
Published: November 2011

AbstractThe total antioxidant capacity of edible oils corresponds to the integrated action of antioxidant compounds. The antioxidant capacity may be used as a proxy of the chemical antioxidant activities of components in oils, but this hypothesis has not been tested by multivariate statistical analysis. Tocols, fatty acids, artificial antioxidants, peroxide value, conjugated dienes, and total antioxidant capacity were determined in samples of refined oils of soybean, corn, canola, and sunflower. Generalized linear models and multiple regression models were adjusted to estimate the integrated association between the total antioxidant capacity and chemical components of oils. The generalized linear model of antioxidant capacity better adjusted to the data because the descriptive variable type of oil was a significant predictor. The type of oil, γ‐ and δ‐tocopherols, and peroxide value explained 95% of the variability of antioxidant capacity in the model (p = 0.0006). Besides, γ‐tocopherol was the most important predictor variable for the model considering the p‐value and the estimated relative weight for the model. Therefore, γ‐tocopherol was the major determinant of total antioxidant capacity of refined oils of soybean, corn, canola, and sunflower.Practical applications: Direct spectrophotometric assay of antioxidant activity can be used to determine the antioxidant quality of fresh refined oils. Furthermore, the statistical evaluation of chemical determinants of vegetable oils based on generalized linear models might contribute to our understanding of the antioxidant quality and the stability of oils.
A Mild Titanium‐Catalyzed Synthesis of Functionalized Amino Coumarins as Fluorescence Labels
Authors: Wirtz Lisa , Kazmaier Uli 
Published: November 2011

AbstractIn contrast to Brønsted and other Lewis acids ClTi(OiPr)3 is especially suited to catalyze the formation of amino‐substituted coumarins from aminophenols and functionalized β‐oxo esters in a Pechmann condensation. This straightforward protocol allows the synthesis of fluorescence labels and false fluorescent neurotransmitters.
Coloured Artefacts Formed by Oxidation of Benzene‐1,2,4‐triol and β‐Dopa During the Extraction of Cortinarius violaceus (Agaricales) with Alcohols
Authors: von Nussbaum Franz , Rüth Matthias , Spiteller Peter , Hübscher‐Weissert Tina , Löbermann Florian , Polborn Kurt , Steglich Wolfgang 
Published: November 2011

AbstractAn array of coloured artefacts was formed upon extraction of the mushroom Cortinarius violaceus with methanol. The structures of these pigments were determined by spectroscopic investigations, including NMR and mass spectrometric analyses. Cortiviolate A and dihydrocortiviol A arise by oxidative dimerization of benzene‐1,2,4‐triol, and cortiviolate B is formed by an unprecedented oxidative rearrangement of β‐dopa. The oxidations are caused by iron(III) ions, released from the iron complex of (R)‐β‐dopa – the native violet pigment of the mushroom. In the course of these investigations, syntheses of the cortiviolates, dihydrocortiviol A, gomphilactone, and two related dilactones were carried out.
Ruthenium‐Catalyzed Sequential Enyne Cross‐Metathesis/ATRA Reactions
Authors: Kiefer Gregor , Ruiz Jesus , Solari Euro , Hilt Gerhard , Severin Kay 
Published: November 2011

AbstractSequential enyne cross‐metathesis reactions of arylalkynes with ethylene followed by atom transfer radical addition (ATRA) with ethyl dichloroacetate or dichloroacetonitrile provide 1,5‐dichloropent‐2‐ene derivatives. The second‐generation Grubbs alkylidene complex [RuCl2(=CHPh)(PCy3)(NHC)] [NHC = 1,3‐bis(2,4,6‐trimethylphenyl)‐2‐imidazolidinylidene] is used as the catalyst precursor for both reactions. Preliminary results show that the reaction products can be converted into vinylcyclopropanes by dechlorination with magnesium or manganese.
One‐Pot Conversion of Serine Derivatives and Amino Sugars into Oxazine Derivatives of γ‐Aryl‐γ‐(hydroxy)amines
Authors: Boto Alicia , Gallardo Juan A. , Álvarez Eleuterio 
Published: November 2011

AbstractA one‐pot process for the transformation of relatively inexpensive serine derivatives into oxazine derivatives of γ‐aryl‐γ‐hydroxy‐α‐amino acids is described. The reaction preferentially afforded 4,6‐cis oxazines. The method can also be applied to the transformation of amino sugars into highly functionalized oxazines, which are precursors of chiral amines.
Convenient Synthesis and Evaluation of a Heptadentate Bifunctional Ligand for Radioimmunotherapy Applications (Eur. J. Org. Chem. 33/2011)
Authors: Chong Hyun‐Soon , Sun Xiang , Dong Pengfei , Kang Chi Soo 
Published: November 2011

AbstractThe cover picture shows the phase contrast image of colon cancer cells (HT29) taken by a confocal microscope as the background image. Bifunctional ligands are an essential component in the biomedical and radiopharmaceutical application of biologically active metals as cytotoxic agents or imaging probes. We herein present the efficient synthesis and evaluation of the bifunctional ligand C‐NE3TA for antibody‐targeted radiation cancer therapy. The synthetic methods to construct the bifunctional ligand are centered on the regiospecific ring opening of aziridine and the aziridinium cation. Details are discussed in the article by H.‐S. Chong et al. on p. 6641 ff.
Loading techniques for OFDM systems with nonlinear distortion effects
Authors: Araújo Teresa , Dinis Rui 
Published: November 2011

ABSTRACTIn this paper, we study the impact of nonlinear distortion effects on adaptive orthogonal frequency division multiplexing systems. An analytical statistical characterisation of the transmitted signals, which is obtained by taking advantage of the Gaussian‐like nature of the orthogonal frequency division multiplexing signals when the number of subcarriers is high, is included. This statistical characterisation is used to evaluate loading algorithms in the presence of strong nonlinear distortion effects and to redefine loading algorithms taking into account nonlinear distortion issues. Copyright © 2011 John Wiley & Sons, Ltd.
Are Analysts' Loss Functions Asymmetric?
Authors: Clatworthy Mark A. , Peel David A. , Pope Peter F. 
Published: November 2011

ABSTRACTDespite displaying a statistically significant optimism bias, analysts' earnings forecasts are an important input to investors’ valuation models. Understanding the possible reasons for any bias is important if information is to be extracted from earnings forecasts and used optimally by investors. Extant research into the shape of analysts' loss functions explains optimism bias as resulting from analysts minimizing the mean absolute forecast error under symmetric, linear loss functions. When the distribution of earnings outcomes is skewed, optimalforecasts can appear biased. In contrast, research into analysts' economic incentives suggests that positive and negative earnings forecast errors made by analysts are not penalized or rewarded symmetrically, suggesting that asymmetric loss functions are an appropriate characterization. To reconcile these findings, we exploit results from economic theory relating to the Linex loss function to discriminate between the symmetric linear loss and the asymmetric loss explanations of analyst forecast bias. Under asymmetric loss functions optimal forecasts will appear biased even if earnings outcomes are symmetric. Our empirical results support the asymmetric loss function explanation. Further analysis also reveals that forecast bias varies systematically across firm characteristics that capture systematic variation in the earnings forecast error distribution. Copyright © 2011 John Wiley & Sons, Ltd.
Space‐Time Model versus VAR Model: Forecasting Electricity demand in Japan
Authors: Ohtsuka Yoshihiro , Kakamu Kazuhiko 
Published: November 2011

ABSTRACTThis paper examined the forecasting performance of disaggregated data with spatial dependency and applied it to forecasting electricity demand in Japan. We compared the performance of the spatial autoregressive ARMA (SAR‐ARMA) model with that of the vector autoregressive (VAR) model from a Bayesian perspective. With regard to the log marginal likelihood and log predictive density, the VAR(1) model performed better than the SAR‐ARMA( 1,1) model. In the case of electricity demand in Japan, we can conclude that the VAR model with contemporaneous aggregation had better forecasting performance than the SAR‐ARMA model. Copyright © 2011 John Wiley & Sons, Ltd.