52 research outputs found

    Acute phase inflammation is characterized by rapid changes in plasma/peritoneal fluid N-glycosylation in mice.

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    To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.Murine zymosan-induced peritonitis is a widely used model for studying the molecular and cellular events responsible for the initiation, persistence and/or resolution of inflammation. Among these events, it is becoming increasingly evident that changes in glycosylation of proteins, especially in the plasma and at the site of inflammation, play an important role in the inflammatory response. Using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS)-based glycosylation profiling, we investigated the qualitative and quantitative effect of zymosan-induced peritonitis on N-glycosylation in mouse plasma and peritoneal fluid. Our results show that both N-glycomes exhibit highly similar glycosylation patterns, consisting mainly of diantennary and triantennary complex type N-glycans with high levels (>95 %) of galactosylation and sialylation (mostly NeuGc) and a medium degree of core fucosylation (30 %). Moreover, MS/MS structural analysis, assisted by linkage-specific derivatization of sialic acids, revealed the presence of O-acetylated sialic acids as well as disialylated antennae ("branching sialylation") characterized by the presence of α2-6-linked NeuGc on the GlcNAc of the NeuGcα2-3-Galβ1-3-GlcNAc terminal motif. A significant decrease of (core) fucosylation together with an increase of both α2-3-linked NeuGc and "branching sialylation" were observed in N-glycomes of mice challenged with zymosan, but not in control mice injected with PBS. Importantly, substantial changes in glycosylation were already observed 12 h after induction of peritonitis, thereby demonstrating an unexpected velocity of the biological mechanisms involved.Dutch Arthritis Association (Reumafonds) LLP-24 Innovative Medicines Initiative Joint Undertaking (IMI JU)/ 115142-2 Netherlands Genomic Initiative/93511033 info:eu-repo/grantAgreement/EC/FP7/278535info:eu-repo/grantAgreement/EC/FP7/27853

    Service Oriented Big Data Management for Transport

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    International audienceThe increasing power of computer hardware and the sophistication of computer software have brought many new possibilities to information world. On one side the possibility to analyse massive data sets has brought new insight, knowledge and information. On the other, it has enabled to massively distribute computing and has opened to a new programming paradigm called Service Oriented Computing particularly well adapted to cloud computing. Applying these new technologies to the transport industry can bring new understanding to town transport infrastructures. The objective of our work is to manage and aggregate cloud services for managing big data and assist decision making for transport systems. Thus this paper presents our approach to propose a service oriented architecture for big data analytics for transport systems based on the cloud. Proposing big data management strategies for data produced by transport infra‐ structures, whilst maintaining cost effective systems deployed on the cloud, is a promising approach. We present the advancement for developing the Data acquisition service and Information extraction and cleaning service as well as the analysis for choosing a sharding strategy

    Seizure protein 6 controls glycosylation and trafficking of kainate receptor subunits GluK2 and GluK3

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    Seizure protein 6 (SEZ6) is required for the development and maintenance of the nervous system, is a major substrate of the protease BACE1 and is linked to Alzheimer's disease (AD) and psychiatric disorders, but its molecular functions are not well understood. Here, we demonstrate that SEZ6 controls glycosylation and cell surface localization of kainate receptors composed of GluK2/3 subunits. Loss of SEZ6 reduced surface levels of GluK2/3 in primary neurons and reduced kainate-evoked currents in CA1 pyramidal neurons in acute hippocampal slices. Mechanistically, loss of SEZ6 in vitro and in vivo prevented modification of GluK2/3 with the human natural killer-1 (HNK-1) glycan, a modulator of GluK2/3 function. SEZ6 interacted with GluK2 through its ectodomain and promoted post-endoplasmic reticulum transport of GluK2 in the secretory pathway in heterologous cells and primary neurons. Taken together, SEZ6 acts as a new trafficking factor for GluK2/3. This novel function may help to better understand the role of SEZ6 in neurologic and psychiatric diseases

    Drug-Resistant Tuberculosis Control in China: Progress and Challenge

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    Background: China has the second highest caseload of multidrug-resistant tuberculosis (MDR-TB) in the world. In 2009, the Chinese government agreed to draw up a plan for MDR-TB prevention and control in the context of a comprehensive health system reform launched in the same year. Discussion: China is facing high prevalence rates of drug-resistant TB and MDR-TB. MDR-TB disproportionally affects the poor rural population and the highest rates are in less developed regions largely due to interrupted and/or inappropriate TB treatment. Most households with an affected member suffer a heavy financial burden because of a combination of treatment and other related costs. The influential Global Fund programme for MDR-TB control in China provides technical and financial support for MDR-TB diagnosis and treatment. However, this programme has a fixed timeline and cannot provide a long term solution. In 2009, the Bill and Melinda Gates Foundation, in cooperation with the National Health and Family Planning Commission of China, started to develop innovative approaches to TB/MDR-TB management and case-based payment mechanisms for treatment, alongside increased health insurance benefits for patients, in order to contain medical costs and reduce financial barriers to treatment. Although these efforts appear to be in the right direction, they may not be sufficient unless (a) domestic sources are mobilized to raise funding for TB/MDR-TB prevention and control and (b) appropriate incentives are given to both health facilities and their care providers. Summary: Along with the on-going Chinese health system reform, sustained government financing and social health protection schemes will be critical to ensure universal access to appropriate TB treatment in order to reduce risk of developing MDR-TB and systematic MDR-TB treatment and management

    Improving the reach of vaccines to low-resource regions, with a needle-free vaccine delivery device and long-term thermostabilization

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    Dry-coated microprojections can deliver vaccine to abundant antigen-presenting cells in the skin and induce efficient immune responses and the dry-coated vaccines are expected to be thermostable at elevated temperatures. In this paper, we show that we have dramatically improved our previously reported gas-jet drying coating method and greatly increased the delivery efficiency of coating from patch to skin to from 6.5% to 32.5%, by both varying the coating parameters and removing the patch edge. Combined with our previous dose sparing report of influenza vaccine delivery in a mouse model, the results show that we now achieve equivalent protective immune responses as intramuscular injection (with the needle and syringe), but with only 1/30th of the actual dose. We also show that influenza vaccine coated microprojection patches are stable for at least 6 months at 23 degrees C. inducing comparable immunogenicity with freshly coated patches. The dry-coated microprojection patches thus have key and unique attributes in ultimately meeting the medical need in certain low-resource regions with low vaccine affordability and difficulty in maintaining "cold-chain" for vaccine storage and transport. (C) 2011 Elsevier B.V. All rights reserved

    Factors Associated with Hepatitis B Testing Among Vietnamese Americans

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    Chronic hepatitis B and hepatitis B-associated liver cancer is a major health disparity among Vietnamese Americans, who have a chronic hepatitis B prevalence rate of 7–14% and an incidence rate for liver cancer six times that of non-Latino whites. Describe factors associated with hepatitis B testing among Vietnamese Americans. A population-based telephone survey conducted in 2007–2008. Vietnamese Americans age 18–64 and living in the Northern California and Washington, DC areas (N = 1,704). Variables included self-reports of sociodemographics, health care factors, and hepatitis B-related behaviors, knowledge, beliefs, and communication with others. The main outcome variable was self-reported receipt of hepatitis B testing. The cooperation rate was 63.1% and the response rate was 27.4%. Only 62% of respondents reported having received a hepatitis B test and 26%, hepatitis B vaccination. Only 54% knew that hepatitis B could be transmitted by sexual intercourse. In multivariable analyses, factors negatively associated with testing included: age 30–49 years, US residence for >10 years, less Vietnamese fluency, lower income, and believing that hepatitis B can be deadly. Factors positively associated with testing included: Northern California residence, having had hepatitis B vaccination, having discussed hepatitis B with family/friends, and employer requested testing. Physician recommendation of hepatitis B testing (OR 4.46, 95% CI 3.36, 5.93) and respondent's request for hepatitis B testing (OR 8.37, 95% CI 5.95, 11.78) were strongly associated with test receipt. Self-reports of hepatitis B testing among Vietnamese Americans remain unacceptably low. Physician recommendation and patient request were the factors most strongly associated with test receipt. A comprehensive effort is needed to promote hepatitis B testing in this population, including culturally-targeted community outreach, increased access to testing, and physician education

    Control of iron deficiency anemia in low- and middle-income countries

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    C1 - Journal Articles RefereedDespite worldwide economic and scientific development, more than a quarter of the world's population remains anemic, and about half of this burden is a result of iron deficiency anemia (IDA). IDA is most prevalent among preschool children and women. Among women, iron supplementation improves physical and cognitive performance, work productivity, and well-being, and iron during pregnancy improves maternal, neonatal, infant, and even long-term child outcomes. Among children, iron may improve cognitive, psychomotor, and physical development, but the evidence for this is more limited. Strategies to control IDA include daily and intermittent iron supplementation, home fortification with micronutrient powders, fortification of staple foods and condiments, and activities to improve food security and dietary diversity. The safety of routine iron supplementation in settings where infectious diseases, particularly malaria, are endemic remains uncertain. The World Health Organization is revising global guidelines for controlling IDA. Implementation of anemia control programs in developing countries requires careful baseline epidemiologic evaluation, selection of appropriate interventions that suit the population, and ongoing monitoring to ensure safety and effectiveness. This review provides an overview and an approach for the implementation of public health interventions for controlling IDA in low- and middle-income countries, with an emphasis on current evidence-based recommendations
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