Soluble RAGE: a hot new biomarker for the hot joint?

The receptor for advanced glycation endproducts (RAGE) interacts with distinct ligand families linked to the inflammatory response. Studies in animal models suggest that RAGE is upregulated in the inflamed joint and that blockade of the receptor, using a ligand decoy soluble form of RAGE (sRAGE), attenuates joint inflammation and expression of inflammatory and tissue-destructive mediators. In this issue of Arthritis Research & Therapy, Rille Pullerits and colleagues reported that plasma levels of sRAGE were reduced in subjects with rheumatoid arthritis compared with healthy controls or subjects with non-inflammatory joint disease. These findings suggest the possibility that levels of sRAGE might be a biomarker of inflammation. Not resolved by these studies, however, is the intriguing possibility that endogenously higher levels of sRAGE might be linked to a lower incidence of arthritis or to the extent of inflammation. Nevertheless, although 'cause or effect' relationships may not be established in this report, fascinating insights into RAGE, inflammation and human arthritis emerge from these studies

Advisory Councils For Business Colleges: Composition And Utilization

A major challenge facing business colleges is keeping up with the rapid changes in the business world.  Business advisory councils provide an important link between business colleges and the business world.  This study was conducted to gather data on the composition and utilization of these councils.  The results reveal that there is widespread use of advisory councils by business colleges.  The most commonly discussed issues by advisory councils were those dealing with administrative issues and student concerns while faculty issues were the least discussed.  Advisory councils were also perceived as being most effective in addressing administrative and student-related issues

Form und Funktion der doppelten Negation in deutschen Dialekten, mit einem Schwerpunkt im Oberdeutschen

The article gives an overview of the form and function of negative concord in German dialects (Alemannic, Bavarian, Upper Franconian varieties, West Central German, East Central German, West Low German, East Low German, Silesian, East Pomeranian, Low Prussian), with a focus on Upper German. The study is based on spontaneous speech data from the 1950s until the 1980s and shows that negative doubling and negative spread (in German: ‘doppelte Negation mit Satznegation’ and ‘doppelte Negation ohne Satznegation’) are two different negation types, thus there is no correlation between them as generally assumed (Haspelmath 1997; Zeijlstra 2004). Furthermore negative doubling is not obligatory, but seems to be conditioned by pragmatics

Introduction: Language in Contact: Yesterday – Today – Tomorrow

The symposium Language in Contact; Yesterday–Today–Tomorrow took place June 21–23, 2017 and was organized by The Graduate School Language & Literature Munich - Class of Language. Scholars using interdisciplinary approaches were invited to Munich and conveyed both traditional and innovative insights into the vast field of language contact. This included both diachronic (Yesterday) and synchronic contributions (Today) as well as papers discussing the future of contact linguistics (Tomorrow). At the symposium, language contact was defined in a broad sense as the language that emerges when speakers of different languages influence one another’s speech; this brought together multiple areas of linguistic study ranging from language change and language policy to language acquisition and language processing. Key to the conference was connecting what we can learn from past instances of language contact that will help us understand language phenomena in present and future research

Human and great ape red blood cells differ in plasmalogen levels and composition

<p>Abstract</p> <p>Background</p> <p>Plasmalogens are ether phospholipids required for normal mammalian developmental, physiological, and cognitive functions. They have been proposed to act as membrane antioxidants and reservoirs of polyunsaturated fatty acids as well as influence intracellular signaling and membrane dynamics. Plasmalogens are particularly enriched in cells and tissues of the human nervous, immune, and cardiovascular systems. Humans with severely reduced plasmalogen levels have reduced life spans, abnormal neurological development, skeletal dysplasia, impaired respiration, and cataracts. Plasmalogen deficiency is also found in the brain tissue of individuals with Alzheimer disease.</p> <p>Results</p> <p>In a human and great ape cohort, we measured the red blood cell (RBC) levels of the most abundant types of plasmalogens. Total RBC plasmalogen levels were lower in humans than bonobos, chimpanzees, and gorillas, but higher than orangutans. There were especially pronounced cross-species differences in the levels of plasmalogens with a C16:0 moiety at the <it>sn</it>-1 position. Humans on Western or vegan diets had comparable total RBC plasmalogen levels, but the latter group showed moderately higher levels of plasmalogens with a C18:1 moiety at the <it>sn</it>-1 position. We did not find robust sex-specific differences in human or chimpanzee RBC plasmalogen levels or composition. Furthermore, human and great ape skin fibroblasts showed only modest differences in peroxisomal plasmalogen biosynthetic activity. Human and chimpanzee microarray data indicated that genes involved in plasmalogen biosynthesis show cross-species differential expression in multiple tissues.</p> <p>Conclusion</p> <p>We propose that the observed differences in human and great ape RBC plasmalogens are primarily caused by their rates of biosynthesis and/or turnover. Gene expression data raise the possibility that other human and great ape cells and tissues differ in plasmalogen levels. Based on the phenotypes of humans and rodents with plasmalogen disorders, we propose that cross-species differences in tissue plasmalogen levels could influence organ functions and processes ranging from cognition to reproduction to aging.</p

Using electrical resistance networks to enhance performance assessments of water distribution networks

Pressurized fluid-distribution networks are strategic elements of civil infrastructure. In the case of fresh-water distribution networks, where leaks are common and where real performance is unknown, advanced sensor-based diagnostic methodologies have the potential to provide enhanced management support. A structural identification methodology that has been used successfully for bridges is adapted to a study of a diagnostic methodology for leak detection in water distribution networks. This methodology is based on error-domain model falsification. Using analogies between Ohm’s law and the Hazen-Williams relationship, an electric network model is built to show similarities with hydraulic networks. The first step is to compare simulated values to show similarity of the network behaviour and then to show similarities throughout the diagnostic process. This study establishes the similarity of the behaviour for hydraulic and electrical networks. It also shows that results obtained with electrical networks are relevant for performance assessments of hydraulic networks. These results present to practicality of studying generic electrical networks of varying size and shape to illustrate the usefulness of the diagnostic methodology for general cases

Performance comparison of reduced models for leak detection in water distribution networks

This paper presents a methodology for comparing the performance of model-reduction strategies to be used with a diagnostic methodology for leak detection in water distribution networks. The goal is to find reduction strategies that are suitable for error-domain model falsification, a model based data interpretation methodology. Twelve reduction strategies are derived from five strategy categories. Categories differ according to the manner in which nodes are selected for deletion. A node is selected for deletion according to: (1) the diameter of the pipes; (2) the number of pipes linked to a node; (3) the angle of the pipes in the case of two-pipe nodes; (4) the distribution of the water demand; and, (5) a pair-wise combination of some categories. The methodology is illustrated using part of a real network. Performance is evaluated first by judging the equivalency of the reduced network with the initial network (before the application of any reduction procedure) and secondly, by assessing the compatibility with the diagnostic methodology. The results show that for each reduction strategy the equivalency of networks is verified. Computational time can be reduced to less than 20% of the non-reduced network in the best case. Results of diagnostic performance show that the performance decreases when using reduced networks. The reduction strategy with the best diagnostic performance is that based on the angle of two-pipe nodes, with an angle threshold of 165°. In addition, the sensitivity of the performance of the reduced networks to variation in leak intensity is evaluated. Results show that the reduction strategies where the number of nodes is significantly reduced are the most sensitive. Finally this paper describes a Pareto analysis that is used to select the reduction strategy that is a good compromise between reduction of computational time and performance of the diagnosis. In this context, the extension strategy is the most attractive

MicroRNA and metabolomics signatures for adrenomyeloneuropathy disease severity

Adrenomyeloneuropathy (AMN), the slow progressive phenotype of adrenoleukodystrophy (ALD), has no clinical plasma biomarker for disease progression. This feasibility study aimed to determine whether metabolomics and micro-RNA in blood plasma provide a potential source of biomarkers for AMN disease severity. Metabolomics and RNA-seq were performed on AMN and healthy human blood plasma. Biomarker discovery and pathway analyses were performed using clustering, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and regression against patient\u27s clinical Expanded Disability Status Score (EDSS). Fourteen AMN and six healthy control samples were analyzed. AMN showed strong disease-severity-specific metabolic and miRNA clustering signatures. Strong, significant clinical correlations were shown for 7-alpha-hydroxy-3-oxo-4-cholestenoate (7-HOCA) (r (2) = 0.83, p \u3c 0.00001), dehydroepiandrosterone sulfate (DHEA-S; r (2) = 0.82, p \u3c 0.00001), hypoxanthine (r (2) = 0.82, p \u3c 0.00001), as well as miRNA-432-5p (r (2) = 0.68, p \u3c 0.00001). KEGG pathway comparison of mild versus severe disease identified affected downstream systems: GAREM, IGF-1, CALCRL, SMAD2&3, glutathione peroxidase, LDH, and NOS. This feasibility study demonstrates that miRNA and metabolomics are a source of potential plasma biomarkers for disease severity in AMN, providing both a disease signature and individual markers with strong clinical correlations. Network analyses of affected systems implicate differentially altered vascular, inflammatory, and oxidative stress pathways, suggesting disease-severity-specific mechanisms as a function of disease severity