92 research outputs found
Characterizing Width Uniformity by Wave Propagation
This work describes a novel image analysis approach to characterize the
uniformity of objects in agglomerates by using the propagation of normal
wavefronts. The problem of width uniformity is discussed and its importance for
the characterization of composite structures normally found in physics and
biology highlighted. The methodology involves identifying each cluster (i.e.
connected component) of interest, which can correspond to objects or voids, and
estimating the respective medial axes by using a recently proposed wavefront
propagation approach, which is briefly reviewed. The distance values along such
axes are identified and their mean and standard deviation values obtained. As
illustrated with respect to synthetic and real objects (in vitro cultures of
neuronal cells), the combined use of these two features provide a powerful
description of the uniformity of the separation between the objects, presenting
potential for several applications in material sciences and biology.Comment: 14 pages, 23 figures, 1 table, 1 referenc
Results of the First Coincident Observations by Two Laser-Interferometric Gravitational Wave Detectors
We report an upper bound on the strain amplitude of gravitational wave bursts
in a waveband from around 800Hz to 1.25kHz. In an effective coincident
observing period of 62 hours, the prototype laser interferometric gravitational
wave detectors of the University of Glasgow and Max Planck Institute for
Quantum Optics, have set a limit of 4.9E-16, averaging over wave polarizations
and incident directions. This is roughly a factor of 2 worse than the
theoretical best limit that the detectors could have set, the excess being due
to unmodelled non-Gaussian noise. The experiment has demonstrated the viability
of the kind of observations planned for the large-scale interferometers that
should be on-line in a few years time.Comment: 11 pages, 2 postscript figure
A genome-wide association study in multiple system atrophy
Objective: To identify genetic variants that play a role in the pathogenesis of multiple system atrophy
(MSA), we undertook a genome-wide association study (GWAS).
Methods: We performed a GWAS with .5 million genotyped and imputed single nucleotide polymorphisms
(SNPs) in 918 patients with MSA of European ancestry and 3,864 controls. MSA
cases were collected from North American and European centers, one third of which were neuropathologically
confirmed.
Results: We found no significant loci after stringent multiple testing correction. A number of regions
emerged as potentially interesting for follow-up at p , 1 3 1026, including SNPs in the
genes FBXO47, ELOVL7, EDN1, and MAPT. Contrary to previous reports, we found no association
of the genes SNCA and COQ2 with MSA.
Conclusions: We present a GWAS in MSA.We have identified several potentially interesting gene
loci, including the MAPT locus, whose significance will have to be evaluated in a larger sample set.
Common genetic variation in SNCA and COQ2 does not seem to be associated with MSA. In the
future, additional samples of well-characterized patients with MSA will need to be collected to
perform a larger MSA GWAS, but this initial study forms the basis for these next steps
PatchPerPixMatch for automated 3d search of neuronal morphologies in light microscopy
Studies of individual neurons in the Drosophila nervous system are facilitated by transgenic lines that sparsely and repeatably label respective neurons of interest. Sparsity can be enhanced by means of intersectional approaches like the split-GAL4 system, which labels the positive intersection of the expression patterns of two (denser) GAL4 lines. To this end, two GAL4 lines have to be identified as labelling a neuron of interest. Current approaches to tackling this task include visual inspection, as well as automated search in 2d projection images, of single cell multi-color flip-out (MCFO) acquisitions of GAL4 expression patterns. There is to date no automated method available that performs full 3d search in MCFO imagery of GAL4 lines, nor one that leverages automated reconstructions of the labelled neuron morphologies. To close this gap, we propose PatchPerPixMatch, a fully automated approach for finding a given neuron morphology in MCFO acquisitions of Gen1 GAL4 lines. PatchPerPixMatch performs automated instance segmentation of MCFO acquisitions, and subsequently searches for a target neuron morphology by minimizing an objective that aims at covering the target with a set of well-fitting segmentation fragments. PatchPerPixMatch is computationally efficient albeit being full 3d, while also highly robust to inaccuracies in the automated neuron instance segmentation. We are releasing PatchPerPixMatch search results for ~30,000 neuron morphologies from the Drosophila hemibrain in ~20,000 MCFO acquisitions of ~3,500 Gen1 GAL4 lines
TDP-43 in the hypoglossal nucleus identifies amyotrophic lateral sclerosis in behavioral variant frontotemporal dementia
The hypoglossal nucleus was recently identified as a key brain region in which the presence of TDP-43 pathology could accurately discriminate TDP-43 proteinopathy cases with clinical amyotrophic lateral sclerosis (ALS). The objective of the present study was to assess the hypoglossal nucleus in behavioral variant frontotemporal dementia (bvFTD), and determine whether TDP-43 in this region is associated with clinical ALS. Twenty-nine cases with neuropathological FTLD-TDP and clinical bvFTD that had not been previously assessed for hypoglossal TDP-43 pathology were included in this study. Of these 29 cases, 41% (n = 12) had a dual diagnosis of bvFTD-ALS at presentation, all 100% (n = 12) of which demonstrated hypoglossal TDP-43 pathology. Of the 59% (n = 17) cohort that presented with pure bvFTD, 35% (n = 6) were identified with hypoglossal TDP-43 pathology. Review of the case files of all pure bvFTD cases revealed evidence of possible or probable ALS in 5 of the 6 hypoglossal-positive cases (83%) towards the end of disease, and this was absent from all cases without such pathology. In conclusion, the present study validates grading the presence of TDP-43 in the hypoglossal nucleus for the pathological identification of bvFTD cases with clinical ALS, and extends this to include the identification of cases with possible ALS at end-stage
Mendelian randomization implies no direct causal association between leukocyte telomere length and amyotrophic lateral sclerosis
Funder: QingLan Research Project of Jiangsu for Outstanding Young TeachersFunder: Project funded by Postdoctoral Science Foundation of Xuzhou Medical UniversityFunder: Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) for Xuzhou Medical UniversityAbstract: We employed Mendelian randomization (MR) to evaluate the causal relationship between leukocyte telomere length (LTL) and amyotrophic lateral sclerosis (ALS) with summary statistics from genome-wide association studies (n = ~ 38,000 for LTL and ~ 81,000 for ALS in the European population; n = ~ 23,000 for LTL and ~ 4,100 for ALS in the Asian population). We further evaluated mediation roles of lipids in the pathway from LTL to ALS. The odds ratio per standard deviation decrease of LTL on ALS was 1.10 (95% CI 0.93–1.31, p = 0.274) in the European population and 0.75 (95% CI 0.53–1.07, p = 0.116) in the Asian population. This null association was also detected between LTL and frontotemporal dementia in the European population. However, we found that an indirect effect of LTL on ALS might be mediated by low density lipoprotein (LDL) or total cholesterol (TC) in the European population. These results were robust against extensive sensitivity analyses. Overall, our MR study did not support the direct causal association between LTL and the ALS risk in neither population, but provided suggestive evidence for the mediation role of LDL or TC on the influence of LTL and ALS in the European population
Split-QF System for Fine-Tuned Transgene Expression in Drosophila
The Q-system is a binary expression system that works well across species. Here, we report the development and demonstrate the applications of a split-QF system that drives strong expression in Drosophila, is repressible by QS, and is inducible by a small nontoxic molecule (quinic acid). The split-QF system is fully compatible with existing split-GAL4 and split-LexA lines, thus greatly expanding the range of possible advanced intersectional experiments and anatomical, physiological, and behavioral assays in Drosophila, and in other organisms
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