327 research outputs found

    Differences in GlycA and lipoprotein particle parameters may help distinguish acute kawasaki disease from other febrile illnesses in children.

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    BackgroundGlycosylation patterns of serum proteins, such as α1-acid glycoprotein, are modified during an acute phase reaction. The response of acute Kawasaki disease (KD) patients to IVIG treatment has been linked to sialic acid levels on native IgG, suggesting that protein glycosylation patterns vary during the immune response in acute KD. Additionally, the distribution and function of lipoprotein particles are altered during inflammation. Therefore, the aim of this study was to explore the potential for GlycA, a marker of protein glycosylation, and the lipoprotein particle profile to distinguish pediatric patients with acute KD from those with other febrile illnesses.MethodsNuclear magnetic resonance was used to quantify GlycA and lipoprotein particle classes and subclasses in pediatric subjects with acute KD (n = 75), post-treatment subacute (n = 36) and convalescent (n = 63) KD, as well as febrile controls (n = 48), and age-similar healthy controls (n = 48).ResultsGlycA was elevated in acute KD subjects compared to febrile controls with bacterial or viral infections, IVIG-treated subacute and convalescent KD subjects, and healthy children (P <0.0001). Acute KD subjects had increased total and small low density lipoprotein particle numbers (LDL-P) (P <0.0001) and decreased total high density lipoprotein particle number (HDL-P) (P <0.0001) compared to febrile controls. Consequently, the ratio of LDL-P to HDL-P was higher in acute KD subjects than all groups tested (P <0.0001). While GlycA, CRP, erythrocyte sedimentation rate, LDL-P and LDL-P/HDL-P ratio were able to distinguish patients with KD from those with other febrile illnesses (AUC = 0.789-0.884), the combinations of GlycA and LDL-P (AUC = 0.909) or GlycA and the LDL-P/HDL-P ratio (AUC = 0.910) were best at discerning KD in patients 6-10 days after illness onset.ConclusionsHigh levels of GlycA confirm enhanced protein glycosylation as part of the acute phase response in KD patients. When combined with common laboratory tests and clinical characteristics, GlycA and NMR-measured lipoprotein particle parameters may be useful for distinguishing acute KD from bacterial or viral illnesses in pediatric patients

    Oidium longipes, a new powdery mildew fungus on petunia in the USA: A potential threat to ornamental and vegetable solanaceous crops

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    This is the first North American report of Oidium longipes, an anamorphic powdery mildew species described recently in Europe. It was found on vegetatively propagated petunia grown in a commercial greenhouse in New Jersey, USA, where it caused a rapidly spreading disease. The pathogen might have originated offshore and may have already been distributed in the United States through horticultural trade. During field surveys in Europe, it was found on petunia in Hungary and Austria as well; this is the first report of O. longipes from these two countries. A detailed light microscopy study of American and European specimens of O. longipes, including freshly collected samples and authentic herbarium specimens, revealed that its conidiophore morphology is more variable than illustrated in the original species description or in subsequent works. Microcycle conidiation, a process not yet known to occur in powdery mildews, was repeatedly observed in O. longipes. The rDNA internal transcribed spacer (ITS) sequences were identical in colonies containing different conidiophore types as well as in a total of five specimens collected from petunia in the United States, Austria, Hungary, Germany, and Switzerland. A phylogenetic analysis of the ITS sequences revealed that the closest known relative of O. longipes is O. lycopersici, known to infect tomato only in Australia. Cross-inoculation tests showed that O. longipes from petunia heavily infected tobacco cv. Xanthi, while the tomato and eggplant cultivars tested were moderately susceptible to this pathogen. These results indicate that its spread represents a potential danger to a number of solanaceous crops. Our ad hoc field surveys conducted in 2006 and 2007 did not detect it outside New Jersey in the United States; all the other powdery mildew–infected petunias, collected in New York and Indiana, were infected by Podosphaera xanthii. In Europe, most of the powdery mildew–infected petunias examined in this study were infected by P. xanthii or Golovinomyces orontii. Our multiple inoculation tests revealed that the same petunia plants and even the same leaves can be infected concomitantly by O. longipes, O. neolycopersici, G. orontii, and P. xanthii. Thus, it is at present unclear to what extent O. longipes contributes to the powdery mildew epidemics that develop year after year on solanaceous plants in many parts of the world

    Inflammatory glycoproteins in cardiometabolic disorders, autoimmune diseases and cancer

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    AbstractThe physiological function initially attributed to the oligosaccharide moieties or glycans on inflammatory glycoproteins was to improve protein stability. However, it is now clear that glycans play a prominent role in glycoprotein structure and function and in some cases contribute to disease states. In fact, glycan processing contributes to pathogenicity not only in autoimmune disorders but also in atherosclerotic cardiovascular disease, diabetes and malignancy. While most clinical laboratory tests measure circulating levels of inflammatory proteins, newly developed diagnostic and prognostic tests are harvesting the information that can be gleaned by measuring the amount or structure of the attached glycans, which may be unique to individuals as well as various diseases. As such, these newer glycan-based tests may provide future means for more personalized approaches to patient stratification and improved patient care.Here we will discuss recent progress in high-throughput laboratory methods for glycomics (i.e. the study of glycan structures) and glycoprotein quantification by methods such as mass spectrometry and nuclear magnetic resonance spectroscopy. We will also review the clinical utility of glycoprotein and glycan measurements in the prediction of common low-grade inflammatory disorders including cardiovascular disease, diabetes and cancer, as well as for monitoring autoimmune disease activity

    Mismatch repair causes the dynamic release of an essential DNA polymerase from the replication fork

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/86887/1/MMI_7841_sm_SuppInfor.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/86887/2/j.1365-2958.2011.07841.x.pd

    Symmetric and asymmetric action integration during cooperative object manipulation in virtual environments

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    Cooperation between multiple users in a virtual environment (VE) can take place at one of three levels. These are defined as where users can perceive each other (Level 1), individually change the scene (Level 2), or simultaneously act on and manipulate the same object (Level 3). Despite representing the highest level of cooperation, multi-user object manipulation has rarely been studied. This paper describes a behavioral experiment in which the piano movers' problem (maneuvering a large object through a restricted space) was used to investigate object manipulation by pairs of participants in a VE. Participants' interactions with the object were integrated together either symmetrically or asymmetrically. The former only allowed the common component of participants' actions to take place, but the latter used the mean. Symmetric action integration was superior for sections of the task when both participants had to perform similar actions, but if participants had to move in different ways (e.g., one maneuvering themselves through a narrow opening while the other traveled down a wide corridor) then asymmetric integration was superior. With both forms of integration, the extent to which participants coordinated their actions was poor and this led to a substantial cooperation overhead (the reduction in performance caused by having to cooperate with another person)

    Ketone Bodies Are Mildly Elevated in Subjects with Type 2 Diabetes Mellitus and Are Inversely Associated with Insulin Resistance as Measured by the Lipoprotein Insulin Resistance Index

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    Background: Quantifying mildly elevated ketone bodies is clinically and pathophysiologically relevant, especially in the context of disease states as well as for monitoring of various diets and exercise regimens. As an alternative assay for measuring ketone bodies in the clinical laboratory, a nuclear magnetic resonance (NMR) spectroscopy-based test was developed for quantification of beta-hydroxybutyrate (beta-HB), acetoacetate (AcAc) and acetone. Methods: The ketone body assay was evaluated for precision, linearity and stability and method comparisons were performed. In addition, plasma ketone bodies were measured in the Insulin Resistance Atherosclerosis Study (IRAS, n = 1198; 373 type 2 diabetes mellitus (T2DM) subjects). Results: beta-HB and AcAc quantified using NMR and mass spectrometry and acetone quantified using NMR and gas chromatography/mass spectrometry were highly correlated (R-2 = 0.996, 0.994, and 0.994 for beta-HB, AcAc, acetone, respectively). Coefficients of variation (%CVs) for intra- and inter-assay precision ranged from 1.3% to 9.3%, 3.1% to 7.7%, and 3.8% to 9.1%, for beta-HB, AcAc and acetone, respectively. In the IRAS, ketone bodies were elevated in subjects with T2DM versus non-diabetic individuals (p = 0.011 t
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