ATF3 upregulation in glia during Wallerian degeneration: differential expression in peripheral nerves and CNS white matter

Background: Many changes in gene expression occur in distal stumps of injured nerves but the transcriptional control of these events is poorly understood. We have examined the expression of the transcription factors ATF3 and c-Jun by non-neuronal cells during Wallerian degeneration following injury to sciatic nerves, dorsal roots and optic nerves of rats and mice, using immunohistochemistry and in situ hybridization.Results: Following sciatic nerve injury-transection or transection and reanastomosis-ATF3 was strongly upregulated by endoneurial, but not perineurial cells, of the distal stumps of the nerves by 1 day post operation (dpo) and remained strongly expressed in the endoneurium at 30 dpo when axonal regeneration was prevented. Most ATF3+ cells were immunoreactive for the Schwann cell marker, S100. When the nerve was transected and reanastomosed, allowing regeneration of axons, most ATF3 expression had been downregulated by 30 dpo. ATF3 expression was weaker in the proximal stumps of the injured nerves than in the distal stumps and present in fewer cells at all times after injury. ATF3 was upregulated by endoneurial cells in the distal stumps of injured neonatal rat sciatic nerves, but more weakly than in adult animals. ATF3 expression in transected sciatic nerves of mice was similar to that in rats. Following dorsal root injury in adult rats, ATF3 was upregulated in the part of the root between the lesion and the spinal cord (containing Schwann cells), beginning at 1 dpo, but not in the dorsal root entry zone or in the degenerating dorsal column of the spinal cord. Following optic nerve crush in adult rats, ATF3 was found in some cells at the injury site and small numbers of cells within the optic nerve displayed weak immunoreactivity. The pattern of expression of c-Jun in all types of nerve injury was similar to that of ATF3.Conclusion: These findings raise the possibility that ATF3/c-Jun heterodimers may play a role in regulating changes in gene expression necessary for preparing the distal segments of injured peripheral nerves for axonal regeneration. The absence of the ATF3 and c-Jun from CNS glia during Wallerian degeneration may limit their ability to support regeneration

Examining the concordance of retinal ganglion cell counts generated using measures of structure and function

PURPOSE: There are several indirect methods used to estimate retinal ganglion cell (RGC) count in an individual eye, but there is limited information as to the agreement between these methods. In this work, RGC receptive field (RGC‐RF) count underlying a spot stimulus (0.43°, Goldmann III) was calculated and compared using three different methods. METHODS: RGC‐RF count was calculated at a retinal eccentricity of 2.32 mm for 44 healthy adult participants (aged 18–58 years, refractive error −9.75 DS to +1.75 DS) using: (i) functional measures of achromatic peripheral grating resolution acuity (PGRA), (ii) structural measures of RGC‐layer thickness (OCT‐model, based on the method outlined by Raza and Hood) and (iii) scaling published histology density data to simulate a global expansion in myopia (Histology‐Balloon). RESULTS: Whilst average RGC‐RF counts from the OCT‐model (median 105.3, IQR 99.6–111.0) and the Histology‐Balloon model (median 107.5, IQR 97.7–114.6) were similar, PGRA estimates were approximately 65% lower (median 37.7, IQR 33.8–46.0). However, there was poor agreement between all three methods (Bland–Altman 95% limits of agreement; PGRA/OCT: 55.4; PGRA/Histology‐Balloon 59.3; OCT/Histology‐Balloon: 52.4). High intersubject variability in RGC‐RF count was evident using all three methods. CONCLUSIONS: The lower PGRA RGC‐RF counts may be the result of targeting only a specific subset of functional RGCs, as opposed to the coarser approach of the OCT‐model and Histology‐Balloon, which include all RGCs, and also likely displaced amacrine cells. In the absence of a ‘ground truth’, direct measure of RGC‐RF count, it is not possible to determine which method is most accurate, and each has limitations. However, what is clear is the poor agreement found between the methods prevents direct comparison of RGC‐RF counts between studies utilising different methodologies and highlights the need to utilise the same method in longitudinal work

Numerical Hermitian Yang-Mills Connections and Kahler Cone Substructure

We further develop the numerical algorithm for computing the gauge connection of slope-stable holomorphic vector bundles on Calabi-Yau manifolds. In particular, recent work on the generalized Donaldson algorithm is extended to bundles with Kahler cone substructure on manifolds with h^{1,1}>1. Since the computation depends only on a one-dimensional ray in the Kahler moduli space, it can probe slope-stability regardless of the size of h^{1,1}. Suitably normalized error measures are introduced to quantitatively compare results for different directions in Kahler moduli space. A significantly improved numerical integration procedure based on adaptive refinements is described and implemented. Finally, an efficient numerical check is proposed for determining whether or not a vector bundle is slope-stable without computing its full connection.Comment: 38 pages, 10 figure

Temporal summation in myopia and its implications for the investigation of glaucoma

Purpose We have previously demonstrated the upper limit of complete spatial summation (Ricco's area) to increase in non-pathological axial myopia compared to non-myopic controls. This study sought to investigate whether temporal summation is also altered in axial myopia to determine if this aspect of visual function, like in glaucoma, is influenced by reductions in retinal ganglion cell (RGC) density. Methods Achromatic contrast thresholds were measured for a GIII-equivalent stimulus (0.43° diameter) of six different stimulus durations (1–24 frames, 1.1–187.8 ms) in 24 participants with axial myopia (mean spherical refractive error: −4.65D, range: −1.00D to −11.25D, mean age: 34.1, range: 21–57 years) and 21 age-similar non-myopic controls (mean spherical refractive error: +0.87D, range: −0.25D to +2.00D, mean age: 31.0, range: 18–55 years). Measurements were performed at 10° eccentricity along the 90°, 180°, 270° and 360° meridians on an achromatic 10 cd/m2 background. The upper limit of complete temporal summation (critical duration, CD) was estimated from the data with iterative two-phase regression analysis. Results There was no significant difference (p = 0.90, Mann–Whitney U-test) in median CD between myopes (median: 44.3 ms; IQR: 26.5, 51.2) and non-myopes (median: 41.6 ms; IQR: 27.3, 48.5). Despite RGC numbers underlying the stimulus being significantly lower in the myopic group (p < 0.001), no relationship was observed between the CD estimate and co-localised RGC number (Pearson's r = −0.13, p = 0.43) or ocular length (Pearson's r = −0.08, p = 0.61). Conclusions Unlike spatial summation, temporal summation is unchanged in myopia. This contrasts with glaucoma where both temporal and spatial summation are altered. As such, perimetric methods optimised to test for anomalies of temporal summation may provide a means to differentiate between conditions causing only a reduced RGC density (e.g., myopia), and pathological processes causing both a reduced RGC density and RGC dysfunction (e.g., glaucoma)

HoloCam: A subsea holographic camera for recording marine organisms and particles

The HoloCam system is a major component of a multi-national multi-discipline project known as HoloMar (funded by the European Commission under the MAST III initiative). The project is concerned with the development of pulsed laser holography to analyse and monitor the populations of living organisms and inanimate particles within the world's oceans. We describe here the development, construction and evaluation of a prototype underwater camera, the purpose of which is to record marine organisms and particles, in-situ. Recording using holography provides several advantages over conventional sampling methods in that it allows non-intrusive, non-destructive, high-resolution imaging of large volumes (up to 10^5 cm^3) in three dimensions. The camera incorporates both in-line and off-axis holographic techniques, which allows particles from a few micrometres to tens of centimetres to be captured. In tandem with development of the HoloCam, a dedicated holographic replay system and an automated data extraction and image processing facility are being developed. These will allow, optimisation of the images recorded by the camera, identification of species and particle concentration plotting

Metrics with Prescribed Ricci Curvature near the Boundary of a Manifold

Suppose $M$ is a manifold with boundary. Choose a point $o\in\partial M$. We investigate the prescribed Ricci curvature equation \Ric(G)=T in a neighborhood of $o$ under natural boundary conditions. The unknown $G$ here is a Riemannian metric. The letter $T$ in the right-hand side denotes a (0,2)-tensor. Our main theorems address the questions of the existence and the uniqueness of solutions. We explain, among other things, how these theorems may be used to study rotationally symmetric metrics near the boundary of a solid torus $\mathcal T$. The paper concludes with a brief discussion of the Einstein equation on $\mathcal T$.Comment: 13 page

Zeta potentials of the rare earth element fluorcarbonate minerals focusing on bastnäsite and parisite

Rare earth elements (REE) are critical to a wide range of technologies ranging from mobile phones to wind turbines. Processing and extraction of REE minerals from ore bodies is, however, both challenging and relatively poorly understood, as the majority of deposits contain only limited enrichment of REEs. An improved understanding of the surface properties of the minerals is important in informing and optimising their processing, in particular for separation by froth flotation. The measurement of zeta potential can be used to extract information regarding the electrical double layer, and hence surface properties of these minerals. There are over 34 REE fluorcarbonate minerals currently identified, however bastnäsite, synchysite and parisite are of most economic importance. Bastnäsite-(Ce), the most common REE fluorcarbonate, supplies over 50% of the world's REE. Previous studies of bastnäsite have showed a wide range of surface behaviour, with the iso-electric point (IEP), being measured between pH values of 4.6 and 9.3. In contrast, no values of IEP have been reported for parisite or synchysite. In this work, we review previous studies of the zeta potentials of bastnäsite to investigate the effects of different methodologies and sample preparation. In addition, measurements of zeta potentials of parisite under water, collector and supernatant conditions were conducted, the first to be reported. These results showed an iso-electric point for parisite of 5.6 under water, with a shift to a more negative zeta potential with both collector (hydroxamic and fatty acids) and supernatant conditions. The IEP with collectors and supernatant was <3.5. As zeta potential measurements in the presence of reagents and supernatants are the most rigorous way of determining the efficiency of a flotation reagent, the agreement between parisite zeta potentials obtained here and previous work on bastnäsite suggests that parisite may be processed using similar reagent schemes to bastnäsite. This is important for future processing of REE deposits, comprising of more complex REE mineralogy

Investigating the Linkage Between Mesopic Spatial Summation and Variations in Retinal Ganglion Cell Density Across the Central Visual Field:Mesopic Spatial Summation with Eccentricity

Purpose The relationship between perimetric stimulus area and Ricco's area (RA) determines measured thresholds and the sensitivity of perimetry to retinal disease. The nature of this relationship, in addition to effect of retinal ganglion cell (RGC) number on this, is currently unknown for the adaptation conditions of mesopic microperimetry. In this study, achromatic mesopic spatial summation was measured across the central visual field to estimate RA with the number of RGCs underlying RA also being established. Methods Achromatic luminance thresholds were measured for six incremental spot stimuli (0.009–2.07 deg2) and 190.4 ms duration, at four locations, each at 2.5°, 5° and 10° eccentricity in five healthy observers (mean age 61.4 years) under mesopic conditions (background 1.58 cd/m2). RA was estimated using two-phase regression analysis with the number of RGCs underlying RA being calculated using normative histological RGC counts. Results Ricco's area exhibited a small but statistically insignificant increase between 2.5° and 10° eccentricity. Compared with photopic conditions, RA was larger, with the difference between RA and the Goldmann III stimulus (0.43°) being minimised. RGC number underlying RA was also higher than reported for photopic conditions (median 70 cells, IQR 36–93), with no significant difference being observed across test locations. Conclusions Ricco's area and the number of RGCs underlying RA do not vary significantly across the central visual field in mesopic conditions. However, RA is larger and more similar to the standard perimetric Goldmann III stimulus under mesopic compared with photopic adaptation conditions. Further work is required to determine if compensatory enlargements in RA occur in age-related macular degeneration, to establish the optimal stimulus parameters for AMD-specific microperimetry