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33 result(s) for "Miller, F.D."
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Axon diameter and axonal transport: In vivo and in vitro effects of androgens
Testosterone is a sex hormone involved in brain maturation via multiple molecular mechanisms. Previous human studies described age-related changes in the overall volume and structural properties of white matter during male puberty. Based on this work, we have proposed that testosterone may induce a radial growth of the axon and, possibly, modulate axonal transport. In order to determine whether this is the case we have used two different experimental approaches. With electron microscopy, we have evaluated sex differences in the structural properties of axons in the corpus callosum (splenium) of young rats, and tested consequences of castration carried out after weaning. Then we examined in vitro the effect of the non-aromatizable androgen Mibolerone on the structure and bidirectional transport of wheat-germ agglutinin vesicles in the axons of cultured sympathetic neurons. With electron microscopy, we found robust sex differences in axonal diameter (males>females) and g ratio (males>females). Removal of endogenous testosterone by castration was associated with lower axon diameter and lower g ratio in castrated (vs. intact) males. In vitro, Mibolerone influenced the axonal transport in a time- and dose-dependent manner, and increased the axon caliber as compared with vehicle-treated neurons. These findings are consistent with the role of testosterone in shaping the axon by regulating its radial growth, as predicted by the initial human studies. •In humans, volume and properties of white matter change during male adolescence.•Here we show that axons are thicker in male than female rats.•Castration at weaning eliminates this structural sex difference.•Synthetic testosterone affects axonal transport in vitro.
Neurotrophin signalling pathways regulating neuronal apoptosis
Recent evidence indicates that naturally occurring neuronal death in mammals is regulated by the interplay between receptor-mediated prosurvival and proapoptotic signals. The neurotrophins, a family of growth factors best known for their positive effects on neuronal biology, have now been shown to mediate both positive and negative survival signals, by signalling through the Trk and p75 neurotrophin receptors, respectively. The mechanisms whereby these two neurotrophin receptors interact to determine neuronal survival have been difficult to decipher, largely because both can signal independently or coincidentally, depending upon the cell or developmental context. Nonetheless, the past several years have seen significant advances in our understanding of this receptor signalling system. In this review, we focus on the proapoptotic actions of the p75 neurotrophin receptor (p75NTR), and on the interplay between Trk and p75NTR that determines neuronal survival.
A New Member of the Clover Proliferation Phytoplasma Group (16SrVI) Associated with Elm Yellows in Illinois
A disease with symptoms similar to elm yellows (EY) was noticed in the early 1990s in suburban Chicago, IL. More than 1,000 mature American elms (Ulmus americana) have since died. Infected trees varied in the incidence and severity of canopy yellowing, leaf epinasty, butterscotch discoloration, and wintergreen odor of the phloem, but all developed a sparse and clumpy crown, uniformly necrotic phloem, and died within 2 years of showing canopy symptoms. Because symptoms were expressed irregularly and phytoplasma detection results by a commercial diagnostic company were inconsistent, a study was initiated to determine if EY phytoplasma was the causal agent. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods using universal or EY phytoplasma specific primers were employed to detect putative phytoplasma(s) associated with 10 trees of varied disease severity within the outbreak region and 10 asymptomatic trees from an uninfected area (controls). Nested PCR using universal primers revealed that 90% of trees from the outbreak region were positive for phytoplasma while asymptomatic elms from another location (controls) tested negative. Phytoplasma-positive trees ranged in disease severity from 1 (asymptomatic) to 5 (near death). Inner bark samples chiseled from the lower trunk had higher phytoplasma detection rates than foliage or drill shavings. RFLP analyses and DNA sequencing of 16S rDNA indicated that the phytoplasma recovered from dying elms in Arlington Heights is not related to the reference EY phytoplasma (group16SrV). It is most closely related to clover proliferation (CP) phy-toplasma (group 16SrVI), and we have designated it Illinois Elm Yellows (ILEY) phytoplasma, and assigned it to a new taxonomic subgroup (16SrVI-C). EY phytoplasma was not detected in any samples, but two ILEY phytoplasma positive trees also were positive for aster yellows (AY) phytoplasma. ILEY phytoplasma was not detected in local leafhopper populations trapped in elm trees between May and September 2000. This is the first report of a phytoplasma related to CP phytoplasma causing elm yellows disease symptoms.
THE FLARING PERIODICITY OF COMET SCHWASSMANN-WACHMANN (1)
The recurrence of brightness flares of Comet Schwassmann-Wachmann (1) reported by Vsekhsvyatskij and attributed by him to persistent sources of solar corpuscular radiation, may reflect, at least in part, the influence of lunar phase on comet observations.
Contemporary Political and Social Philosophy
Reynolds reviews 'Contemporary Political and Social Philosophy' edited by Ellen Frankel Paul, Fred D. Miller Jr, and Jeffrey Paul.
Tensor image registration library: Deformable registration of stand‐alone histology images to whole‐brain post‐mortem MRI data
•New software framework for prototyping bespoke image registration pipelines.•Configurable pipeline to register stand-alone histology sections to whole-brain MRI.•Novel deformable slice-to-volume registration algorithm.•No strict necessity for serial histological sectioning for MRI-histology registration. Accurate registration between microscopy and MRI data is necessary for validating imaging biomarkers against neuropathology, and to disentangle complex signal dependencies in microstructural MRI. Existing registration methods often rely on serial histological sampling or significant manual input, providing limited scope to work with a large number of stand-alone histology sections. Here we present a customisable pipeline to assist the registration of stand-alone histology sections to whole-brain MRI data. Our pipeline registers stained histology sections to whole-brain post-mortem MRI in 4 stages, with the help of two photographic intermediaries: a block face image (to undistort histology sections) and coronal brain slab photographs (to insert them into MRI space). Each registration stage is implemented as a configurable stand-alone Python script using our novel platform, Tensor Image Registration Library (TIRL), which provides flexibility for wider adaptation. We report our experience of registering 87 PLP-stained histology sections from 14 subjects and perform various experiments to assess the accuracy and robustness of each stage of the pipeline. All 87 histology sections were successfully registered to MRI. Histology-to-block registration (Stage 1) achieved 0.2–0.4 mm accuracy, better than commonly used existing methods. Block-to-slice matching (Stage 2) showed great robustness in automatically identifying and inserting small tissue blocks into whole brain slices with 0.2 mm accuracy. Simulations demonstrated sub-voxel level accuracy (0.13 mm) of the slice-to-volume registration (Stage 3) algorithm, which was observed in over 200 actual brain slice registrations, compensating 3D slice deformations up to 6.5 mm. Stage 4 combined the previous stages and generated refined pixelwise aligned multi-modal histology-MRI stacks. Our open-source pipeline provides robust automation tools for registering stand-alone histology sections to MRI data with sub-voxel level precision, and the underlying framework makes it readily adaptable to a diverse range of microscopy-MRI studies.
Over the Coffee
DEAR PRESIDENT: Well, sir, I thought of yon as I was watching the Navy-Penn football game. These modern quarterbacks are so deft at handling the ball, they use what they call \"deception\" on every play, so an amateur like me can't tell who's carrying it, or which way they're running.
An automated pipeline for extracting histological stain area fraction for voxelwise quantitative MRI-histology comparisons
•Automated pipeline to generate quantitative maps from immunohistochemical stains.•Pipeline is generalisable to stains targeting multiple microstructures.•Pipeline addresses key artefacts related to tissue staining and digitisation.•Perform voxelwise comparisons, relating microscopy to multimodal MRI.•Results highlight the importance of analysing multiple stains when validating MRI. The acquisition of MRI and histology in the same post-mortem tissue sample enables direct correlation between MRI and histologically-derived parameters. However, there still lacks a standardised automated pipeline to process histology data, with most studies relying on manual intervention. Here, we introduce an automated pipeline to extract a quantitative histological measure for staining density (stain area fraction, SAF) from multiple immunohistochemical (IHC) stains. The pipeline is designed to directly address key IHC artefacts related to tissue staining and slide digitisation. Here, the pipeline was applied to post-mortem human brain data from multiple subjects, relating MRI parameters (FA, MD, RD, AD, R2*, R1) to IHC slides stained for myelin, neurofilaments, microglia and activated microglia. Utilising high-quality MRI-histology co-registrations, we then performed whole-slide voxelwise comparisons (simple correlations, partial correlations and multiple regression analyses) between multimodal MRI- and IHC-derived parameters. The pipeline was found to be reproducible, robust to artefacts and generalisable across multiple IHC stains. Our partial correlation results suggest that some simple MRI-SAF correlations should be interpreted with caution, due to the co-localisation of other tissue features (e.g., myelin and neurofilaments). Further, we find activated microglia—a generic biomarker of inflammation—to consistently be the strongest predictor of high DTI FA and low RD, which may suggest sensitivity of diffusion MRI to aspects of neuroinflammation related to microglial activation, even after accounting for other microstructural changes (demyelination, axonal loss and general microglia infiltration). Together, these results show the utility of this approach in carefully curating IHC data and performing multimodal analyses to better understand microstructural relationships with MRI. [Display omitted]