The ubiquitin proteasome system in glia and its role in neurodegenerative diseases

The ubiquitin proteasome system (UPS) is crucial for intracellular protein homeostasis and for degradation of aberrant and damaged proteins. The accumulation of ubiquitinated proteins is a hallmark of many neurodegenerative diseases, including amyotrophic lateral sclerosis, Alzheimer's, Parkinson's, and Huntington's disease, leading to the hypothesis that proteasomal impairment is contributing to these diseases. So far, most research related to the UPS in neurodegenerative diseases has been focused on neurons, while glial cells have been largely disregarded in this respect. However, glial cells are essential for proper neuronal function and adopt a reactive phenotype in neurodegenerative diseases, thereby contributing to an inflammatory response. This process is called reactive gliosis, which in turn affects UPS function in glial cells. In many neurodegenerative diseases, mostly neurons show accumulation and aggregation of ubiquitinated proteins, suggesting that glial cells may be better equipped to maintain proper protein homeostasis. During an inflammatory reaction, the immunoproteasome is induced in glia, which may contribute to a more efficient degradation of disease-related proteins. Here we review the role of the UPS in glial cells in various neurodegenerative diseases, and we discuss how studying glial cell function might provide essential information in unraveling mechanisms of neurodegenerative diseases

Development of analysis techniques for the use of aerial photography in the monitoring of intertidal mussel beds and oyster beds

This project aimed at improving the analysis techniques of aerial photography for mussel bed recognition and mapping. In this project two techniques were tested; recognition and mapping by human eye and recognition and mapping by automatic detection software. The detection with the human eye was tested in two ways. The first test considered recognition of mussel beds in an area were contours of the previous year were available. The second test concerned a blind recognition test without any knowledge on previous locations of mussel beds

Future Burden and Costs of Smoking-Related Disease in the Netherlands: A Dynamic Modeling Approach

AbstractObjectivesIn this article, we explore the future health gain of different policy measures to reduce smoking prevalence: health education campaigns specifically aimed at keeping (young) people from starting to smoke, campaigns aimed at persuading smokers to quit, and tax measures.MethodsWe drew up different policy scenarios based on evaluations of several health promotion campaigns. Implementing these into the dynamic multistate models, we simulated smoking prevalence, loss of life-years, and costs for several decades into the next century.ResultsIn the short run, campaigns aimed at potential “quitters” appear to be most effective in terms of health gain. However, their effect fades away after several decades, while campaigns aimed at young “starters” or tax measures in the end yield a larger and more lasting decrease in smoking attributable disease burden.ConclusionDynamic modeling is very useful tool in calculating costs and effects of preventive public health measures

All-electron GW calculation based on the LAPW method: application to wurtzite ZnO

We present a new, all-electron implementation of the GW approximation and apply it to wurtzite ZnO. Eigenfunctions computed in the local-density approximation (LDA) by the full-potential linearized augmented-plane-wave (LAPW) or the linearized muffin-tin-orbital (LMTO) method supply the input for generating the Green function G and the screened Coulomb interaction W. A mixed basis is used for the expansion of W, consisting of plane waves in the interstitial region and augmented-wavefunction products in the augmentation-sphere regions. The frequency-dependence of the dielectric function is computed within the random-phase approximation (RPA), without a plasmon-pole approximation. The Zn 3d orbitals are treated as valence states within the LDA; both core and valence states are included in the self-energy calculation. The calculated bandgap is smaller than experiment by about 1eV, in contrast to previously reported GW results. Self-energy corrections are orbital-dependent, and push down the deep O 2s and Zn 3d levels by about 1eV relative to the LDA. The d level shifts closer to experiment but the size of shift is underestimated, suggesting that the RPA overscreens localized states.Comment: 10 pages, 3 figures, submitted to Phys. Rev.

Identification of risk factors in minimally invasive surgery: a prospective multicenter study

Development and application of statistical models for medical scientific researc

Laparoscopic hysterectomy for benign indications: clinical practice guideline

Cervix cance

IgA N- and O-glycosylation profiling reveals no association with the pregnancy-related improvement in rheumatoid arthritis

Background: The Fc glycosylation of immunoglobulin G (IgG) is well known to associate with rheumatoid arthritis (RA) disease activity. The same may be true for other classes of Igs. In the present study, we sought to determine whether the glycosylation of IgA was different between healthy subjects and patients with RA, as well as whether it was associated with RA disease activity, in particular with the pregnancy-associated improvement thereof or the flare after delivery. Methods: A recently developed high-throughput method for glycoprofiling of IgA1 was applied to affinity-captured IgA from sera of patients with RA (n = 252) and healthy control subjects (n = 32) collected before, during and after pregnancy. Results: IgA1 O-glycans bore more sialic acids in patients with RA than in control subjects. In addition, levels of bisecting N-acetylglucosamine of the N-glycans at asparagine 144 were higher in the patients with RA. The levels of several N-glycosylation traits were shown to change with pregnancy, similar to what has been shown before for IgG. However, the changes in IgA glycosylation were not associated with improvement or a flare of disease activity. Conclusions: The glycosylation of IgA differs between patients with RA and healthy control subjects. However, our data suggest only a minor, if any, association of IgA glycosylation with RA disease activity

Phytanoyl-CoA hydroxylase from rat liver: protein purification and cDNA cloning with implications for the subcellular localization of phytanic acid alpha-oxidation

Phytanoyl-CoA hydroxylase (PhyH) catalyzes the conversion of phytanoyl-CoA to 2-hydroxyphytanoyl-CoA, which is the first step in the phytanic acid alpha-oxidation pathway. Recently, several studies have shown that in humans, phytanic acid alpha-oxidation is localized in peroxisomes. In rat, however, the alpha-oxidation pathway has been reported to be mitochondrial. In order to clarify this differential subcellular distribution, we have studied the rat PhyH protein. We have purified PhyH from rat liver to apparent homogeneity as judged by SDS-PAGE. Sequence analysis of two PhyH peptide fragments allowed cloning of the rat PHYH cDNA encoding a 38. 6 kDa protein. The deduced amino acid sequence revealed strong homology to human PhyH including the presence of a peroxisome targeting signal type 2 (PTS2). Heterologous expression of rat PHYH in Saccharomyces cerevisiae yielded a 38.6 kDa protein whereas the PhyH purified from rat liver had a molecular mass of 35 kDa. This indicates that PhyH is probably processed in rat by proteolytic removal of a leader sequence containing the PTS2. This type of processing has been reported in several other peroxisomal proteins that contain a PTS2. Subcellular localization studies using equilibrium density centrifugation showed that PhyH is indeed a peroxisomal protein in rat. The finding that PhyH is peroxisomal in both rat and humans provides strong evidence against the concept of a differential subcellular localization of phytanic acid alpha-oxidation in rat and huma

Psychometrics of the observational scales of the Utrecht Scale for Evaluation of Rehabilitation (USER): Content and structural validity, internal consistency and reliability: A study on psychometric properties of the USER.

Introduction: : Establish content and structural validity, internal consistency, inter-rater reliability, and measurement error of the physical and cognitive scales of the Utrecht Scale for Evaluation clinical Rehabilitation (USER) in geriatric rehabilitation. Material and methods: : First, an expert consensus-meeting (N=7) was organised for content validity wherein scale content validity index (CVI) was measured. Second, in a sample of geriatric rehabilitation patient structural validity (N=616) was assessed by confirmatory factor analyses for exploring unidimensionality. Cut-off criteria were: Root Mean Square Error of Approximation (RMSEA) 0.95. Local independence (residual correlation0.30 and Hs-coefficient >0.50) were also calculated. Cronbach alphas were calculated for internal consistency. Alpha's > 0.7 was considered adequate. T hird, two nurses independently administered the USER to 37 patients. Intraclass-correlation coefficients (ICC) were calculated for inter-rater reliability (IRR), standard error of measurement (SEM) and Smallest Detectable Change (SDC). Results: : The CVI for physical functioning was moderate (0.73) and excellent for cognitive functioning (0.97). Structural validity physical scale was acceptable (CFI;0.95, TLI;0.93, RMSEA;0.07, ECV;0.78, OmegaH;0.87; Monotonicity;(Hi;0.52-0.75 and Hs;0.63)). Cognitive scale was good (CFI;0.98, TLI;0.96, RMSEA;0.05, ECV;0.66 and OmegaH;0.90. Monotonicity;(Hi;0.30 -0.70 and Hs;0.61)). Cronbach's alpha were high: physical scale;0.92 and cognitive scale;0.94. Reliability physical scale ICC;0.94, SEM;5 and SDC;14 and cognitive scale ICC;0.88, SEM;5 and SDC;13. Conclusion: : The observational scales of the USER have shown sufficient content and structural validity, internal consistency, and interrater reliability for measuring physical and cognitive function in geriatric rehabilitation. Trial registration: : N/AGeriatrics in primary carePublic Health and primary car