Glucosylsphingosine Is a Highly Sensitive and Specific Biomarker for Primary Diagnostic and Follow-Up Monitoring in Gaucher Disease in a Non-Jewish, Caucasian Cohort of Gaucher Disease Patients

Gaucher disease (GD) is the most common lysosomal storage disorder (LSD). Based on a deficient β-glucocerebrosidase it leads to an accumulation of glucosylceramide. Standard diagnostic procedures include measurement of enzyme activity, genetic testing as well as analysis of chitotriosidase and CCL18/PARC as biomarkers. Even though chitotriosidase is the most well-established biomarker in GD, it is not specific for GD. Furthermore, it may be false negative in a significant percentage of GD patients due to mutation. Additionally, chitotriosidase reflects the changes in the course of the disease belatedly. This further enhances the need for a reliable biomarker, especially for the monitoring of the disease and the impact of potential treatments.Here, we evaluated the sensitivity and specificity of the previously reported biomarker Glucosylsphingosine with regard to different control groups (healthy control vs. GD carriers vs. other LSDs).Only GD patients displayed elevated levels of Glucosylsphingosine higher than 12 ng/ml whereas the comparison controls groups revealed concentrations below the pathological cut-off, verifying the specificity of Glucosylsphingosine as a biomarker for GD. In addition, we evaluated the biomarker before and during enzyme replacement therapy (ERT) in 19 patients, demonstrating a decrease in Glucosylsphingosine over time with the most pronounced reduction within the first 6 months of ERT. Furthermore, our data reveals a correlation between the medical consequence of specific mutations and Glucosylsphingosine.In summary, Glucosylsphingosine is a very promising, reliable and specific biomarker for GD

Grundwasser - Altlasten aktuell

Neun Fachbeiträge dokumentieren die Ergebnisse der aktuellen Projekt- und Forschungsarbeit des Landesamtes im Bereich Grundwasser und Altlasten. Themen sind u. a. diffuse Schwermetallbelastungen in 10 Grundwasserkörpern, die nach Wasserrahmenrichtlinie im schlechten chemischen Zustand ausgewiesen wurden, die Umsetzung der EG-Wasserrahmenrichtlinie in von Punktquellen beeinflussten Grundwasserkörpern und die bisherigen Ergebnisse des internationalen Projektes SHARP. Weitere Beiträge befassen sich mit dem Bearbeitungsstand und dem Handlungsbedarf der im Sächsischen Altlastenkataster (SALKA) erfassten Flächen, dem Gefährdungspotenzial von Gärtnereien und den altlastenbezogenen Bewertungs- und Analyseempfehlungen für kurzkettige Alkylphenole

Genomic, Proteomic and Physiological Characterization of a T5-like Bacteriophage for Control of Shiga Toxin-Producing Escherichia coli O157:H7

Despite multiple control measures, Escherichia coli O157:H7 (STEC O157:H7) continues to be responsible for many food borne outbreaks in North America and elsewhere. Bacteriophage therapy may prove useful for controlling this pathogen in the host, their environment and food. Bacteriophage vB_EcoS_AKFV33 (AKFV33), a T5-like phage of Siphoviridae lysed common phage types of STEC O157:H7 and not non-O157 E. coli. Moreover, STEC O157:H7 isolated from the same feedlot pen from which the phage was obtained, were highly susceptible to AKFV33. Adsorption rate constant and burst size were estimated to be 9.31×10−9 ml/min and 350 PFU/infected cell, respectively. The genome of AKVF33 was 108,853 bp (38.95% G+C), containing 160 open reading frames (ORFs), 22 tRNA genes and 32 strong promoters recognized by host RNA polymerase. Of 12 ORFs without homologues to T5-like phages, 7 predicted novel proteins while others exhibited low identity (<60%) to proteins in the National Centre for Biotechnology Information database. AKVF33 also lacked the L-shaped tail fiber protein typical of T5, but was predicted to have tail fibers comprised of 2 novel proteins with low identity (37–41%) to tail fibers of E. coli phage phiEco32 of Podoviridae, a putative side tail fiber protein of a prophage from E. coli IAI39 and a conserved domain protein of E. coli MS196-1. The receptor-binding tail protein (pb5) shared an overall identify of 29–72% to that of other T5-like phages, with no region coding for more than 6 amino acids in common. Proteomic analysis identified 4 structural proteins corresponding to the capsid, major tail, tail fiber and pore-forming tail tip (pb2). The genome of AKFV33 lacked regions coding for known virulence factors, integration-related proteins or antibiotic resistance determinants. Phage AKFV33 is a unique, highly lytic STEC O157:H7-specific T5-like phage that may have considerable potential as a pre- and post-harvest biocontrol agent

Diversity, Fairness, and Data-Driven Personalization in (News) Recommender System (Dagstuhl Perspectives Workshop 19482)

As people increasingly rely on online media and recommender systems to consume information, engage in debates and form their political opinions, the design goals of online media and news recommenders have wide implications for the political and social processes that take place online and offline. Current recommender systems have been observed to promote personalization and more effective forms of informing, but also to narrow the user’s exposure to diverse content. Concerns about echo-chambers and filter bubbles highlight the importance of design metrics that can successfully strike a balance between accurate recommendations that respond to individual information needs and preferences, while at the same time addressing concerns about missing out important information, context and the broader cultural and political diversity in the news, as well as fairness. A broader, more sophisticated vision of the future of personalized recommenders needs to be formed - a vision that can only be developed as the result of a collaborative effort by different areas of academic research (media studies, computer science, law and legal philosophy, communication science, political philosophy, and democratic theory). The proposed workshop will set first steps to develop such a much needed vision on the role of recommender systems on the democratic role of the media and define the guidelines as well as a manifesto for future research and long-term goals for the emerging topic of fairness, diversity, and personalization in recommender systems

Diversity in News Recommendation

News diversity in the media has for a long time been a foundational and uncontested basis for ensuring that the communicative needs of individuals and society at large are met. Today, people increasingly rely on online content and recommender systems to consume information challenging the traditional concept of news diversity. In addition, the very concept of diversity, which differs between disciplines, will need to be re-evaluated requiring an interdisciplinary investigation, which requires a new level of mutual cooperation between computer scientists, social scientists, and legal scholars. Based on the outcome of a interdisciplinary workshop, we have the following recommendations, directed at researchers, funders, legislators, regulators, and the media industry: - Conduct interdisciplinary research on news recommenders and diversity. - Create a safe harbor for academic research with industry data. - Strengthen the role of public values in news recommenders. - Create a meaningful governance framework for news recommenders. - Fund a joint lab to spearhead the needed interdisciplinary research, boost practical innovation, develop reference solutions, and transfer insights into practice

Gedichte / Goethe, Johann Wolfgang /

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