Capn5 Expression in the Healthy and Regenerating Zebrafish Retina

PURPOSE. Autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV) is a devastating inherited autoimmune disease of the eye that displays features commonly seen in other eye diseases, such as retinitis pigmentosa and diabetic retinopathy. ADNIV is caused by a gain-of-function mutation in Calpain-5 (CAPN5), a calcium-dependent cysteine protease. Very little is known about the normal function of CAPN5 in the adult retina, and there are conflicting results regarding its role during mammalian embryonic development. The zebrafish (Danio rerio) is an excellent animal model for studying vertebrate development and tissue regeneration, and represents a novel model to explore the function of Capn5 in the eye. METHODS. We characterized the expression of Capn5 in the developing zebrafish central nervous system (CNS) and retina, in the adult zebrafish retina, and in response to photoreceptor degeneration and regeneration using whole-mount in situ hybridization, FISH, and immunohistochemistry. RESULTS. In zebrafish, capn5 is strongly expressed in the developing embryonic brain, early optic vesicles, and in newly differentiated retinal photoreceptors. We found that expression of capn5 colocalized with cone-specific markers in the adult zebrafish retina. We observed an increase in expression of Capn5 in a zebrafish model of chronic rod photoreceptor degeneration and regeneration. Acute light damage to the zebrafish retina was accompanied by an increase in expression of Capn5 in the surviving cones and in a subset of Müller glia. CONCLUSIONS. These studies suggest that Capn5 may play a role in CNS development, photoreceptor maintenance, and photoreceptor regeneration

Quantized Hydrodynamics

The object of this paper is to derive Landau's theory of quantized hydrodynamics from the many-particle Schroedinger equation. Landau's results are obtained, together with an additional term in the Hamiltonian

An analysis of the Research Fellowship Scheme of the Royal College of Surgeons of England.

BACKGROUND: The Research Fellowship Scheme of the Royal College of Surgeons of England commenced in 1993 with the aim of exposing selected surgical trainees to research techniques and methodology, with the hope of having an impact on surgical research and increasing the cadre of young surgeons who might decide to pursue an academic career in surgery. Over 11 million pounds sterling (approximately US 20 million dollars) has been invested in 264 fellowships. The College wished to evaluate the impact of the Scheme on the careers of research fellows, surgical research, and patient care. As the 10th anniversary of the Scheme approached. STUDY DESIGN: Two-hundred and sixty research fellows whose current addresses were available were sent a questionnaire. Two-hundred and thirty-eight (91.5%) responded. RESULTS: Three-quarters of the research fellows conducted laboratory-based research, with most of the remainder conducting patient-based clinical research. One-third of the fellows who have reached consultant status have an academic component to their post. The total number of publications based on fellowship projects was 531, with a median impact factor of 3.5. Almost all fellows had been awarded a higher degree or were working toward this. Half of the fellows received subsequent funding for research, mostly awarded by national or international funding bodies. CONCLUSIONS: The Research Fellowship Scheme of the Royal College of Surgeons of England has successfully supported many trainee surgeons in the initial phase of their research career. It has helped surgical research by increasing the pool of surgeons willing to embark on an academic career. Indirectly, patient care has benefited by promoting an evidence-based culture among young surgeons. Such schemes are relevant to surgical training programs elsewhere if more young surgeons are to be attracted into academic surgery

Pair Correlations, Short Range Order and Dispersive Excitations in the Quasi-Kagome Quantum Magnet Volborthite

We present spatial and dynamic information on the s=1/2 distorted kagome antiferromagnet volborthite, Cu3V2O7(OD)2.2D2O, obtained by polarized and inelastic neutron scattering. The instantaneous structure factor, S(Q), is dominated by nearest neighbor pair correlations, with short range order at wave vectors Q1=0.65(3) {\AA}^-1 and Q2=1.15(5) {\AA}^-1 emerging below 5 K. The excitation spectrum, S(Q,{\omega}), reveals two steep branches dispersing from Q1 and Q2, and a flat mode at {\omega}=5.0(2) meV. The results allow us to identify the cross-over at T*=1 K in 51V NMR and specific heat measurements as the build-up of correlations at Q_1. We compare our data to theoretical models proposed for volborthite, and demonstrate that the excitation spectrum can be explained by spin-wave-like excitations with anisotropic exchange parameters, as also suggested by recent local density calculations.Comment: Rewritten article resubmitted to Phys. Rev. Lett. 021

Structural and magnetic study of Yb3+ in the perovskites Sr2YbMO6 (M = Nb, Ta, Sb)

The compounds Sr2YbNbO6, Sr2YbTaO6 and Sr2YbSbO6 have been prepared using solid state methods by heating pelleted reagents in air at temperatures up to 1400°C. Rietveld refinement against room temperature neutron powder diffraction data show that all three compounds crystallise with a cationordered variant of the perovskite structure in the P21/n space group. Complete cation ordering occurs between M5+ and Yb3+ over two octahedrally-coordinated sites in the structure and all compounds are stoichiometric in oxygen. The Sb-O bond lengths are similar to related perovskite compounds but differ slightly from those indicated by bond valence sums. Magnetic susceptibility data resemble Curie-Weiss paramagnetic behaviour, but can be better understood as arising from the effect of the octahedral crystal field on the 2F5/2 ground state of Yb3+ leading to a temperature dependent magnetic moment on this ion below 100 K

Structure and magnetic properties of the cubic oxide fluoride BaFeO2F

Fluorination of the parent oxide, BaFeO3- δ, with polyvinylidine fluoride gives rise to a cubic compound with a = 4.0603(4) Å at 298K. 57Fe Mössbauer spectra confirmed that all the iron is present as Fe3+. Neutron diffraction data showed complete occupancy of the anion sites indicating a composition BaFeO2F, with a large displacement of the iron off-site. The magnetic ordering temperature was determined as TN = 645±5K. Neutron diffraction data at 4.2K established G-type antiferromagnetism with a magnetic moment per Fe3+ ion of 3.95μB. However, magnetisation measurements indicated the presence of a weak ferromagnetic moment which is assigned to the canting of the antiferromagnetic structure. 57Fe Mössbauer spectra in the temperature range 10 to 300K were fitted with a model of fluoride ion distribution that retains charge neutrality of the perovskite unit cel

Is manganese-doped diamond a ferromagnetic semiconductor?

We use density-functional theoretical methods to examine the recent prediction, based on a mean-field solution of the Zener model, that diamond doped by Mn (with spin S=5/2) would be a dilute magnetic semiconductor that remains ferromagnetic well above room temperature. Our findings suggest this to be unlikely, for four reasons: (1) substitutional Mn in diamond has a low-spin S=1/2 ground state; (2) the substitutional site is energetically unfavorable relative to the much larger "divacancy" site; 3) Mn in the divacancy site is an acceptor, but with only hyperdeep levels, and hence the holes are likely to remain localized; (4) the calculated Heisenberg couplings between Mn in nearby divacancy sites are two orders of magnitude smaller than for substitutional Mn in germanium.Comment: 5 pages, 5 figure

Well-mixed plasma and tissue viral populations in RT-SHIV-infected macaques implies a lack of viral replication in the tissues during antiretroviral therapy

Background: Determining the anatomic compartments that contribute to plasma HIV-1 is critical to understanding the sources of residual viremia during combination antiretroviral therapy (ART). We analyzed viral DNA and RNA populations in the plasma and tissues from macaques infected with SIV containing HIV-1 RT (RT-SHIV) to identify possible sources of persistent viremia and to investigate the effect of ART on viral replication in tissues. Tissues were collected at necropsy from four pigtailed macaques infected for 30 weeks with a diverse population of RT-SHIV. Two animals (6760 and 8232) were untreated and two animals (8030 and 8272) were treated with efavirenz, tenofovir, and emtricitabine for 20 weeks. Results: A total of 1800 single-genome RT-SHIV pol and env DNA and RNA sequences were analyzed from the plasma, PBMCs, axillary and mesenteric lymph nodes, spleen, thymus, small intestine, bone marrow, lung, and brain. Analyses of intracellular DNA and RNA populations revealed that the majority of proviruses in tissues from untreated animal 8232 were not expressed, whereas a greater proportion of proviruses in tissues were expressed from 6760. Few intracellular RNA sequences were detected in treated animals and most contained inactivating mutations, such as frame shifts or large deletions. Phylogenetics showed that RT-SHIV DNA populations in tissues were not different from virus in contemporary plasma samples in the treated or untreated animals, demonstrating a lack of anatomic compartmentalization and suggesting that plasma viremia is derived from multiple tissue sources. No sequence divergence was detected in the plasma or between tissues in the treated animals after 20 weeks of ART indicating a lack of ongoing replication in tissues during treatment. Conclusions: Virus populations in plasma and tissues did not differ significantly in either treated or untreated macaques, suggesting frequent exchange of virus or infected cells between tissues and plasma, consistent with non-compartmentalized and widely disseminated infection. There was no genetic evidence of ongoing replication in tissues during suppressive ART