Salivary Diagnostics : Point-of-Care diagnostics of MMP-8 in dentistry and medicine

Peer reviewe

Graphic Organizers in the Social Studies Classroom: Effective Content Integration Tools for Preservice Teachers

Preservice teachers working with elementary school teachers in university practicum settings often report limited time for social studies instruction because of increased accountability for mathematics and reading achievement via No Child Left Behind. Incorporating content literacy tools such as graphic organizers with social studies learning can be an effective means for integrating these content areas. The author shares results of a university project describing preservice teachers use of graphic organizers during content reading instruction in practicum classroom settings

Principals and School Factors That Impact Elementary School Student Achievement

This study examined principals and school factors associated with elementary school student achievement. Nine predictor variables were analyzed to determine their impact on student state assessment scores: (a) years of principal experience, (b) years of teaching experience by the principal, (c) years of principal experience at present site, (d) highest level of education by the principal, (e) principal gender, (f) principal leadership as measured by the three subscales of the Principal Instructional Management Rating Scale, and (g) free/reduced lunch population at the school. Study findings are discussed

Ordinary Gamers - The Vanishing Violence In War Games And Its Influence On Male Gamers

War games often try to simulate the characteristics of real weapons - their range, loading times and the bullets’ caliber in order to create an authentic image of war. What they do not show is its authentic violence. Usually we do not see blood pixels and splatter orgies as in dungeon games in which the player has to fight monsters and zombies with eg. magic swords. Instead pictures of a clean war are presented in which civilians hardly ever appear and every weapon hits the target remote-controlled. Because of the simulation’s naturalism gamers may believe that a genuine war looks like the one the screen - and, in fact, today’s soldiers are not faced with the ‘white in the eye of the enemy’ any longer what they do see are symbols on the radar or abstract objects on a computer screen. Accordingly, the real war more and more looks like a computer game while the computer game increasingly looks like reality. Among the currently most popular war game genres are World War 2 games. They met their renaissance with the 1998 release of Stephen Spielberg’s Hollywood movie “Saving Private Ryan”. The film starts with an impressive staging of the battle following the landing at Omaha Beach in 1944 and subsequently a number of WW2 games were published in which gamers could re-enact the battle over and over on the internet. The respective gamers are organised in so called clans which often refer to historical divisions of Allied forces or German troops. Some of them even play under the names of well-known SS divisions such as “Leibstandarte Adolf Hitler”. Most of the other gamers in this community do not seem to object to SS-clans who argue that they were only re-enacting their idols’ campaigns and did not share their biologist and racist world view. Thus, they try to promote the image of the bravely fighting SS-soldier in disregard of the war crimes committed by the Waffen-SS. Such arguments resemble the patterns used in speeches of the German Neo-Nazi party NPD. In my article, I will analyse popular war games and the way they try to advance the image of the brave soldier and a intriguing weapon technology while neglecting the effects of violence and atrocities and how these games do not appear in the daily discussion about violence and are mostly elided by the protection of minors

Parkinson's disease-linked mutations in VPS35 induce dopaminergic neurodegeneration

Mutations in the vacuolar protein sorting 35 homolog (VPS35) gene at the PARK17 locus, encoding a key component of the retromer complex, were recently identified as a new cause of late-onset, autosomal dominant Parkinson's disease (PD). Here we explore the pathogenic consequences of PD-associated mutations in VPS35 using a number of model systems. VPS35 exhibits a broad neuronal distribution throughout the rodent brain, including within the nigrostriatal dopaminergic pathway. In the human brain, VPS35 protein levels and distribution are similar in tissues from control and PD subjects, and VPS35 is not associated with Lewy body pathology. The common D620N missense mutation in VPS35 does not compromise its protein stability or localization to endosomal and lysosomal vesicles, or the vesicular sorting of the retromer cargo, sortilin, SorLA and cation-independent mannose 6-phosphate receptor, in rodent primary neurons or patient-derived human fibroblasts. In yeast we show that PD-linked VPS35 mutations are functional and can normally complement VPS35 null phenotypes suggesting that they do not result in a loss-of-function. In rat primary cortical cultures the overexpression of human VPS35 induces neuronal cell death and increases neuronal vulnerability to PD-relevant cellular stress. In a novel viral-mediated gene transfer rat model, the expression of D620N VPS35 induces the marked degeneration of substantia nigra dopaminergic neurons and axonal pathology, a cardinal pathological hallmark of PD. Collectively, these studies establish that dominant VPS35 mutations lead to neurodegeneration in PD consistent with a gain-of-function mechanism, and support a key role for VPS35 in the development of PD

Accumulation of lysosulfatide in the brain of arylsulfatase A-deficient mice

Lysosomal storage diseases are a group of disorders where accumulation of catabolites is manifested in the lysosomes of different cell types. In metachromatic leukodystrophy (Arylsulfatase A [EC.3.1.6.8] deficiency) storage of the glycosphingolipid sulfatide in the brain leads to demyelination, resulting in neuromotor co-ordination deficits and regression. In a mouse model for metachromatic leukodystrophy, the ASA null mutant mouse, the accumulation of sulfatide in correlation to phenotype has been thoroughly investigated. Another lipid species reported to accumulate in patients with metachromatic leukodystrophy is the sulfatide related lipid lysosulfatide. Lysosulfatide was shown to be a cytotoxic compound in cell culture experiments and thus suggested to be involved in the pathology of metachromatic leukodystrophy. In this study, we further investigated the developmental profile of lysosulfatide in the brain of ASA null mutant mice by using high performance liquid chromatography. Lysosulfatide could be detected in the brain of normal mice (ASA +/+) from 1.8 months up to 23.1 months of age. From the age of 8.8 months the lysosulfatide levels remained constant at 1 pmol/mg wet tissue. The developmental change (< 20 months) of brain lysosulfatide showed an accumulation in ASA null mutant mice at ages above one month compared to its normal counterpart (ASA +/+). Thus, the ASA null mutant mouse might be a suitable model to further investigate the role of lysosulfatide in the pathogenesis of metachromatic leukodystrophy

Fast-dRRT*: Efficient Multi-Robot Motion Planning for Automated Industrial Manufacturing

We present Fast-dRRT*, a sampling-based multi-robot planner, for real-time industrial automation scenarios. Fast-dRRT* builds upon the discrete rapidly-exploring random tree (dRRT*) planner, and extends dRRT* by using pre-computed swept volumes for efficient collision detection, deadlock avoidance for partial multi-robot problems, and a simplified rewiring strategy. We evaluate Fast-dRRT* on five challenging multi-robot scenarios using two to four industrial robot arms from various manufacturers. The scenarios comprise situations involving deadlocks, narrow passages, and close proximity tasks. The results are compared against dRRT*, and show Fast-dRRT* to outperform dRRT* by up to 94% in terms of finding solutions within given time limits, while only sacrificing up to 35% on initial solution cost. Furthermore, Fast-dRRT* demonstrates resilience against noise in target configurations, and is able to solve challenging welding, and pick and place tasks with reduced computational time. This makes Fast-dRRT* a promising option for real-time motion planning in industrial automation.Comment: 7 pages, 6 figures, submitted to ICRA 202

TFEB regulates lysosomal proteostasis

Loss-of-function diseases are often caused by destabilizing mutations that lead to protein misfolding and degradation. Modulating the innate protein homeostasis (proteostasis) capacity may lead to rescue of native folding of the mutated variants, thereby ameliorating the disease phenotype. In lysosomal storage disorders (LSDs), a number of highly prevalent alleles have missense mutations that do not impair the enzyme's catalytic activity but destabilize its native structure, resulting in the degradation of the misfolded protein. Enhancing the cellular folding capacity enables rescuing the native, biologically functional structure of these unstable mutated enzymes. However, proteostasis modulators specific for the lysosomal system are currently unknown. Here, we investigate the role of the transcription factor EB (TFEB), a master regulator of lysosomal biogenesis and function, in modulating lysosomal proteostasis in LSDs. We show that TFEB activation results in enhanced folding, trafficking and lysosomal activity of a severely destabilized glucocerebrosidase (GC) variant associated with the development of Gaucher disease (GD), the most common LSD. TFEB specifically induces the expression of GC and of key genes involved in folding and lysosomal trafficking, thereby enhancing both the pool of mutated enzyme and its processing through the secretory pathway. TFEB activation also rescues the activity of a β-hexosaminidase mutant associated with the development of another LSD, Tay–Sachs disease, thus suggesting general applicability of TFEB-mediated proteostasis modulation to rescue destabilizing mutations in LSDs. In summary, our findings identify TFEB as a specific regulator of lysosomal proteostasis and suggest that TFEB may be used as a therapeutic target to rescue enzyme homeostasis in LSDs

Myelination in the absence of UDP-galactose:ceramide galactosyl-transferase and fatty acid 2 -hydroxylase

<p>Abstract</p> <p>Background</p> <p>The sphingolipids galactosylceramide (GalCer) and sulfatide are major myelin components and are thought to play important roles in myelin function. The importance of GalCer and sulfatide has been validated using UDP-galactose:ceramide galactosyltransferase-deficient (<it>Cgt</it>^-/-) mice, which are impaired in myelin maintenance. These mice, however, are still able to form compact myelin. Loss of GalCer and sulfatide in these mice is accompanied by up-regulation of 2-hydroxylated fatty acid containing (HFA)-glucosylceramide in myelin. This was interpreted as a partial compensation of the loss of HFA-GalCer, which may prevent a more severe myelin phenotype. In order to test this hypothesis, we have generated <it>Cgt</it>^-/-mice with an additional deletion of the fatty acid 2-hydroxylase (<it>Fa2h</it>) gene.</p> <p>Results</p> <p><it>Fa2h</it>^-/-/Cgt^-/-double-deficient mice lack sulfatide, GalCer, and in addition HFA-GlcCer and sphingomyelin. Interestingly, compared to <it>Cgt</it>^-/-mice the amount of GlcCer in CNS myelin was strongly reduced in <it>Fa2h</it>^-/-/<it>Cgt</it>^-/-mice by more than 80%. This was accompanied by a significant increase in sphingomyelin, which was the predominant sphingolipid in <it>Fa2h</it>^-/-/<it>Cgt</it>^-/-mice. Despite these significant changes in myelin sphingolipids, compact myelin was formed in <it>Fa2h</it>^-/-/<it>Cgt</it>^-/-mice, and g-ratios of myelinated axons in the spinal cord of 4-week-old <it>Fa2h</it>^-/-/<it>Cgt</it>^-/-mice did not differ significantly from that of <it>Cgt</it>^-/-mice, and there was no obvious phenotypic difference between <it>Fa2h</it>^-/-/<it>Cgt</it>^-/-and <it>Cgt</it>^-/-mice</p> <p>Conclusions</p> <p>These data show that compact myelin can be formed with non-hydroxylated sphingomyelin as the predominant sphingolipid and suggest that the presence of HFA-GlcCer and HFA-sphingomyelin in <it>Cgt</it>^-/-mice does not functionally compensate the loss of HFA-GalCer.</p