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Neurotransmitters such as glutamate are potential regulators of neurogenesis. Interference with defined glutamate receptor subtypes affects proliferation, migration and differentiation of neural progenitor cells. The cellular targets for the actions of different glutamate receptor ligands are less well known. In this study we have combined calcium imaging, measurement of membrane potential, time‐lapse imaging and immunocytochemistry to obtain a spatial overview of migrating mouse embryonic neural progenitor cell‐derived cells responding to glutamate receptor agonists and antagonists. Responses via metabotropic glutamate receptor 5 correlated with radial glial cells and dominated in the inner migration zones close to the neurosphere. Block of metabotropic glutamate receptor 5 resulted in shorter radial glial processes, a transient increase in neuron‐like cells emerging from the neurosphere and increased motility of neuron‐like cells. α‐Amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA)/kainate receptors are present on the majority of migrating neuronal cells, which with time accumulate at the outer edge of the migration zone. Blocking these receptors leads to an enhanced extension of radial glial processes and a reduced motility of neuron‐like cells. Our results indicate that functional glutamate receptors have profound effects on the motility of neural progenitor cells. The main target for metabotropic glutamate receptor 5 appears to be radial glial cells while AMPA/kainate receptors are mainly expressed in newborn neuronal cells and regulate the migratory progress of these cells. The results suggest that both metabotropic glutamate receptor 5 and AMPA/kainate receptors are of importance for the guidance of migrating embryonic progenitor cells.  相似文献   
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This article describes a combination of interactive classification and super-sampling visualization algorithms that greatly enhances the realism of 3-D reconstructions of the Visible Human data sets. Objects are classified on the basis of ellipsoidal regions in RGB space. The ellipsoids are used for super-sampling in the visualization process.  相似文献   
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Long-term survival is an often used, yet poorly defined, concept in the study of glioblastoma multiforme (GBM). This study suggests a method to define a time-point for long-term survival in patients with GBM. Data for this study were obtained from the Surveillance, Epidemiology and End-Results database, which was limited to the most recent data using the period approach. Relative survival measures were used and modelled using piecewise constant hazards to describe the survival profile of long-term survivors of GBM. For patients with GBM, the first quarter of the second year (5th quarter) post-diagnosis is considered to be the peak incidence of mortality with an excess hazard ratio of 7.58 (95% confidence interval = 6.54, 8.78) and the risk of death due to GBM decreases to half of its rate at 2.5 years post-diagnosis. The 2.5-year cumulative relative survival (CRS) for all patients is approximately 8%, with a CRS of approximately 2% at 10 years. Using the definition of long-term survival suggested here, the results indicate that long-term survivors are patients who survive at least 2.5 years post-diagnosis. The most likely time period for patients with GBM to die is the 5th quarter post-diagnosis.  相似文献   
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By merging neuropsychological (CANTAB/Cambridge Neuropsychological Test Automated Battery) and structural brain imaging data (voxel-based-morphometry) the present study sought to identify the neurocognitive correlates of executive functions in individuals with Asperger syndrome (AS) compared to healthy controls. Results disclosed subtle group differences regarding response speed on only one CANTAB subtest that is thought to tap fronto-executive network functions (SWM/spatial working memory). Across all participants, SWM performance was significantly associated with two brain regions (precentral gyrus white matter, precuneus grey matter), thus suggesting a close link between fronto-executive functions (SWM) and circumscribed fronto-parietal brain structures. Finally, symptom severity (ADOS total score) was best predicted by response speed on a set-shifting task (IES) thought to tap fronto-striatal functions (corrected R2 56 %).  相似文献   
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Hereditary chronic kidney disease (CKD) appears to be more frequent than the clinical perception. Exome sequencing (ES) studies in CKD cohorts could identify pathogenic variants in ~10% of individuals. Tubulointerstitial kidney diseases, showing no typical clinical/histologic finding but tubulointerstitial fibrosis, are particularly difficult to diagnose. We used a targeted panel (29 genes) and MUC1-SNaPshot to sequence 271 DNAs, selected in defined disease entities and age cutoffs from 5217 individuals in the German Chronic Kidney Disease cohort. We identified 33 pathogenic variants. Of these 27 (81.8%) were in COL4A3/4/5, the largest group being 15 COL4A5 variants with nine unrelated individuals carrying c.1871G>A, p.(Gly624Asp). We found three cysteine variants in UMOD, a novel missense and a novel splice variant in HNF1B and the homoplastic MTTF variant m.616T>C. Copy-number analysis identified a heterozygous COL4A5 deletion, and a HNF1B duplication/deletion, respectively. Overall, pathogenic variants were present in 12.5% (34/271) and variants of unknown significance in 9.6% (26/271) of selected individuals. Bioinformatic predictions paired with gold standard diagnostics for MUC1 (SNaPshot) could not identify the typical cytosine duplication (“c.428dupC”) in any individual, implying that ADTKD-MUC1 is rare. Our study shows that >10% of selected individuals carry disease-causing variants in genes partly associated with tubulointerstitial kidney diseases. COL4A3/4/5 genes constitute the largest fraction, implying they are regularly overlooked using clinical Alport syndrome criteria and displaying the existence of phenocopies. We identified variants easily missed by some ES pipelines. The clinical filtering criteria applied enriched for an underlying genetic disorder.Subject terms: End-stage renal disease, Genetics research, Alport syndrome, Nephrosclerosis  相似文献   
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Background/aimsTo evaluate 1-year success rates and safety profile of Preserflo™ Microshunt in glaucoma patients.MethodsRetrospective multicentre cohort study of 100 consecutive eyes (91 patients) from four tertiary-referral glaucoma centres. Four intraocular pressure (IOP) criteria were defined: A: IOP ≤ 21 mmHg+IOP reduction ≥20% from baseline; B: IOP ≤ 18 mmHg+IOP reduction ≥20%; C: IOP ≤ 15 mmHg+IOP reduction ≥25%; D: IOP≤12 mmHg+IOP reduction ≥30%. Success was defined as qualified or complete based on whether reached with or without medication. Primary outcome was success according to the above criteria. Secondary outcomes included: IOP, best-corrected visual acuity (BCVA), medication use, complications, postoperative interventions, and failure-associated factors.ResultsQualified and complete success rates (95% CI) at 12 months were 74%(66–83%) and 58%(49–69%) for criterion A, 72%(63–82%) and 57%(48–68%) for B, 52%(43–63%) and 47%(38–58%) for C, 29%(21–40%) and 26%(19–36%) for D. Overall median (interquartile range (IQR)) preoperative IOP decreased from 21.5(19–28) mmHg to 13(11–16) mmHg at 12 months. BCVA was not significantly different up to 12 months (p = 0.79). Preoperative median (IQR) number of medications decreased from 3 (2–3) to 0 (0–1) at 12 months. Twelve eyes underwent needling, five surgical revision and one device removal due to corneal oedema. There were no hypotony-related complications. Non-Caucasian ethnicity was the only risk factor consistently associated with increased failure.ConclusionsPreserflo™ Microshunt is a viable surgical option in glaucoma patients, with reasonable short-term success rates, decreased medications use, excellent safety profile, smooth postoperative care, and rapid learning curve. Success rates for the most stringent IOP cutoffs were modest, indicating that it may not be the optimal surgery when very low target IOP is required.Subject terms: Outcomes research, Optic nerve diseases  相似文献   
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