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21.
Karin van der Hiele Dennis van Gorp Rob Ruimschotel No?lle Kamminga Leo Visser Huub Middelkoop 《PloS one》2015,10(6)
The majority of patients with Multiple Sclerosis (MS) are unable to retain employment within 10 years from disease onset. Executive abilities, such as planning, working memory, attention, problem solving, inhibition and mental flexibility may have a direct impact on the ability to maintain a job. This study investigated differences in subjective and objective executive abilities between relapsing-remitting MS patients with and without a paid job. We included 55 relapsing-remitting MS patients from a community-based sample (47 females; mean age: 47 years; 36% employed). Patients underwent neurological, cognitive and psychological assessments at their homes, including an extensive executive test battery. We found that unemployed patients had a longer disease duration (t(53)=2.76, p=0.008) and reported more organising and planning problems (χ2(1)=6.3, p=0.012), higher distractibility (Kendall’s tau-b= -0.24, p=0.03) and more cognitive fatigue (U=205.0, p=0.028, r=-0.30) than employed patients. Unemployed patients completed slightly less categories on the Wisconsin Card Sorting Test (U=243.5, p=0.042, r=-0.28). Possible influential factors such as age, educational level, physical functioning, depression and anxiety did not differ between groups. In conclusion, while relapsing-remitting MS patients without a paid job reported more executive problems and cognitive fatigue than patients with a paid job, little differences were found in objective executive abilities. Further research is needed to examine possible causal relations. 相似文献
22.
Konstantinos Nikopoulos Christian Gilissen Alexander Hoischen C. Erik van Nouhuys Ellen A.W. Blokland Nienke Wieskamp Tim M. Strom Mauk A.D. Tilanus Arijit Mukhopadhyay Hans Scheffer Lies H. Hoefsloot Frans P.M. Cremers Rob W.J. Collin 《American journal of human genetics》2010,86(2):240-247
Familial exudative vitreoretinopathy (FEVR) is a genetically heterogeneous retinal disorder characterized by abnormal vascularisation of the peripheral retina, often accompanied by retinal detachment. To date, mutations in three genes (FZD4, LRP5, and NDP) have been shown to be causative for FEVR. In two large Dutch pedigrees segregating autosomal-dominant FEVR, genome-wide SNP analysis identified an FEVR locus of ∼40 Mb on chromosome 7. Microsatellite marker analysis suggested similar at risk haplotypes in patients of both families. To identify the causative gene, we applied next-generation sequencing in the proband of one of the families, by analyzing all exons and intron-exon boundaries of 338 genes, in addition to microRNAs, noncoding RNAs, and other highly conserved genomic regions in the 40 Mb linkage interval. After detailed bioinformatic analysis of the sequence data, prioritization of all detected sequence variants led to three candidates to be considered as the causative genetic defect in this family. One of these variants was an alanine-to-proline substitution in the transmembrane 4 superfamily member 12 protein, encoded by TSPAN12. This protein has very recently been implicated in regulating the development of retinal vasculature, together with the proteins encoded by FZD4, LRP5, and NDP. Sequence analysis of TSPAN12 revealed two mutations segregating in five of 11 FEVR families, indicating that mutations in TSPAN12 are a relatively frequent cause of FEVR. Furthermore, we demonstrate the power of targeted next-generation sequencing technology to identify disease genes in linkage intervals. 相似文献
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Huub Maas Richard T Jaspers Guus C Baan Peter A Huijing 《Journal of applied physiology》2003,95(5):2004-2013
Force transmission from muscle fibers via the connective tissue network (i.e., myofascial force transmission) is an important determinant of muscle function. This study investigates the role of myofascial pathways for force transmission from multitendoned extensor digitorum longus (EDL) muscle within an intact anterior crural compartment. Effects of length changes exclusively of head III of rat EDL muscle (EDL III) on myofascial force transmission were assessed. EDL III was lengthened at the distal tendon. For different lengths of EDL III, isometric forces were measured at the distal tendon of EDL III, as well as at the proximal tendon of whole EDL and at the distal tendons of tibialis anterior and extensor hallucis longus (TA+EHL) muscles. Lengthening of EDL III caused high changes in force exerted at the distal tendon of EDL III (from 0 to 1.03 +/- 0.07 N). In contrast, only minor changes were found in force exerted at the proximal EDL tendon (from 2.37 +/- 0.09 to 2.53 +/- 0.10 N). Increasing the length of EDL III decreased TA+EHL force significantly (by 7%, i.e., from 5.62 +/- 0.27 to 5.22 +/- 0.32 N). These results show that force is transmitted between EDL III and adjacent tissues via myofascial pathways. Optimal force exerted at the distal tendon of EDL III (1.03 +/- 0.07 N) was more than twice the force expected on the basis of the physiological cross-sectional area of EDL III muscle fibers (0.42 N). Therefore, a substantial fraction of this force must originate from sources other than EDL III. It is concluded that myofascial pathways play an important role in force transmission from multitendoned muscles. 相似文献
25.
Membrane fusion requires drastic and transient changes of bilayer curvature and here we have studied the interaction of three de novo designed synthetic hydrophobic peptides with a biomimetic three-lipid mixture by solid state NMR. An experimental approach is presented for screening of peptide-lipid interactions and their aggregation, and their embedding in a biomimetic membrane system using established proton-decoupled 13C, 15N and proton spin diffusion heteronuclear 1H−13C correlation NMR methods at high magnetic field. Experiments are presented for a set of de-novo designed fusion peptides in interaction with their lipid environment. The data provide additional support for the transmembrane model for the least fusogenic peptide, L16, while the peripheral intercalation model is preferred for the fusogenic peptides LV16 and LV16G8P9. This contributes to converging evidence that peripheral intercalation is both necessary and sufficient to trigger the fusion process for a lipid mixture close to a critical point for phase separation across the bilayer. 相似文献
26.
Online biochemical detection of glutathione-S-transferase P1-specific inhibitors in complex mixtures
Kool J Eggink M van Rossum H van Liempd SM van Elswijk DA Irth H Commandeur JN Meerman JH Vermeulen NP 《Journal of biomolecular screening》2007,12(3):396-405
A high-resolution screening (HRS) technology is described, which couples 2 parallel enzyme affinity detection (EAD) systems for substrates and inhibitors of rat cytosolic glutathione-S-transferases (cGSTs) and purified human GST P1 to gradient reversed-phase high-performance liquid chromatography (HPLC). The cGSTs and GST P1 EAD systems were optimized and validated first in flow injection analysis (FIA) mode, and optimized values were subsequently used for HPLC mode. The IC(50) values of 8 ligands thus obtained online agreed well with the IC(50) values obtained with microplate reader-based assays. For ethacrynic acid, an IC(50) value of 1.8 +/- 0.4 microM was obtained with the cGSTs EAD system in FIA mode and 0.8 +/- 0.6 microM in HPLC mode. For ethacrynic acid with the GST P1 EAD system, IC(50) values of 6.0 +/- 2.9 and 3.6 +/- 2.8 microM were obtained in FIA and HPLC modes, respectively. An HRS GST EAD system, consisting of both the cGSTs and the GST P1 EAD system in HPLC mode in parallel, was able to separate complex mixtures of compounds and to determine online their individual affinity for cGSTs and GST P1. Finally, a small library of GST inhibitors, synthesized by reaction of several electrophiles with glutathione (GSH), was successfully screened with the newly developed parallel HRS GST EAD system. It is concluded that the present online gradient HPLC-based HRS screening technology offers new perspectives for sensitive and simultaneous screening of general cGSTs and specific GST P1 inhibitors in mixtures. 相似文献
27.
White spot syndrome virus (WSSV) has been a major cause of shrimp mortality in aquaculture worldwide in the past decades. In this study, WSSV infection (by immersion) and behaviour recruitment of haemocytes is investigated in gills and midgut, using an antiserum against the viral protein VP28 and a monoclonal antibody recognising haemocytes (WSH8) in a double immunohistochemical staining and in addition transmission electron microscopy was applied. More WSH 8(+) haemocytes were detected at 48 and 72 h post-infection in the gills of infected shrimp compared to uninfected animals. Haemocytes in the gills and midgut were not associated with VP28-immunoreactivity. In the gills many other cells showed virus replication in their nuclei, while infected nuclei in the gut cells were rare. Nevertheless, the epithelial cells in the midgut showed a clear uptake of VP28 and accumulation in supranuclear vacuoles (SNV) at 8h post-infection. However, epithelial nuclei were never VP28-immunoreactive and electron microscopy study suggests degradation of viral-like particles in the SNV. In contrast to the gills, the midgut connective tissue shows a clear increase in degranulation of haemocytes, resulting in the appearance of WSH8-immunoreactive thread-like material at 48 and 72 h post-infection. These results indicate recruitment of haemocytes upon immersion infection in the gills and degranulation of haemocytes in less infected organs, like the midgut. 相似文献
28.
Anaerobic ammonium-oxidizing bacteria in marine environments: widespread occurrence but low diversity 总被引:18,自引:0,他引:18
Schmid MC Risgaard-Petersen N van de Vossenberg J Kuypers MM Lavik G Petersen J Hulth S Thamdrup B Canfield D Dalsgaard T Rysgaard S Sejr MK Strous M den Camp HJ Jetten MS 《Environmental microbiology》2007,9(6):1476-1484
Laboratory and field studies have indicated that anaerobic ammonium oxidation (anammox) is an important process in the marine nitrogen cycle. In this study 11 additional anoxic marine sediment and water column samples were studied to substantiate this claim. In a combined approach using the molecular methods, polymerase chain reaction (PCR), qualitative and quantitative fluorescence in situ hybridization (FISH), as well as (15)N stable isotope activity measurements, it was shown that anammox bacteria were present and active in all samples investigated. The anammox activity measured in the sediment samples ranged from 0.08 fmol cell(-1) day(-1) N(2) in the Golfo Dulce (Pacific Ocean, Costa Rica) sediment to 0.98 fmol cell(-1) day(-1) N(2) in the Gullmarsfjorden (North Sea, Sweden) sediment. The percentage of anammox cell of the total population (stained with DAPI) as assessed by quantitative FISH was highest in the Barents Sea (9% +/- 4%) and in most of the samples well over 2%. Fluorescence in situ hybridization and phylogenetic analysis of the PCR products derived from the marine samples indicated the exclusive presence of members of the Candidatus'Scalindua' genus. This study showed the ubiquitous presence of anammox bacteria in anoxic marine ecosystems, supporting previous observations on the importance of anammox for N cycling in marine environments. 相似文献
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