The failure of microglia to digest developmental apoptotic cells contributes to the pathology of RNASET2-deficient leukoencephalopathy

The contribution of microglia in neurological disorders is emerging as a leading disease driver rather than a consequence of pathology. RNAseT2‐deficient leukoencephalopathy is a severe childhood white matter disorder affecting patients in their first year of life and mimicking a cytomegalovirus brain infection. The early onset and resemblance of the symptoms to a viral infection suggest an inflammatory and embryonic origin of the pathology. There are no treatments available for this disease as our understanding of the cellular drivers of the pathology are still unknown. In this study, using a zebrafish mutant for the orthologous rnaset2 gene, we have identified an inflammatory signature in early development and an antiviral immune response in mature adult brains. Using the optical transparency and the ex utero development of the zebrafish larvae we studied immune cell behavior during brain development and identified abnormal microglia as an early marker of pathology. Live imaging and electron microscopy identified that mutant microglia displayed an engorged morphology and were filled with undigested apoptotic cells and undigested substrate. Using microglia‐specific depletion and rescue experiments, we identified microglia as drivers of this embryonic phenotype and potential key cellular player in the pathology of RNAseT2‐deficient leukoencephalopathy. Our zebrafish model also presented with reduced survival and locomotor defects, therefore recapitulating many aspects of the human disease. Our study therefore placed our rnaset2 mutant at the forefront of leukodystrophy preclinical models and highlighted tissue‐specific approaches as future therapeutic avenues

Failure to clear developmental apoptosis contributes to the pathology of RNASET2-deficient leukoencephalopathy

The contribution of microglia in neurological disorders is emerging as a leading driver rather than a consequence of pathology. RNAseT2-deficient leukoencephalopathy is a severe childhood white matter disorder affecting patients in their first year of life and mimics a cytomegalovirus brain infection. The early onset and resemblance of the symptoms to an immune response suggest an inflammatory and embryonic origin of the pathology. In this study, we identify deficient microglia as an early marker of pathology. Using the ex utero development and the optical transparency of an rnaset2-deficient zebrafish model, we found that dysfunctional microglia fail to clear apoptotic neurons during brain development. This was associated with increased number of apoptotic cells and behavioural defects lasting into adulthood. This zebrafish model recapitulates all aspect of the human disease to be used as a robust preclinical model. Using microglia-specific depletion and rescue experiments, we identified microglia as potential drivers of the pathology and highlight tissue-specific approaches as future therapeutic avenues

Chorological and nomenclatural notes on peruvian carex (Cyperaceae)

Here we present relevant records of nine species of the genus Carex (Cyperaceae) new for Peru: C. amicta, C. brehmeri, C. camptoglochin, C. enneastachya, C. livida, C. maritima, C. ownbeyi, C. ruth-satzae, and C. vallis-pulchrae. We perform the lectotypification of the names Carex camptoglochin, C. amicta and C. confertospicata.En este estudio se reconocen nueve registros nuevos de especies del género Carex (Cyperaceae) para la flora del Perú: C. amicta, C. brehmeri, C. camptoglochin, C. enneastachya, C. livida, C. maritima, C. ownbeyi, C. ruthsatzae y C. vallis-pulchrae. También hemos realizado la lectotipificación de los nombres Carex camptoglochin, C. amicta y C. confertospicata

The Degasperis-Procesi equation as a non-metric Euler equation

In this paper we present a geometric interpretation of the periodic Degasperis-Procesi equation as the geodesic flow of a right invariant symmetric linear connection on the diffeomorphism group of the circle. We also show that for any evolution in the family of $b$-equations there is neither gain nor loss of the spatial regularity of solutions. This in turn allows us to view the Degasperis-Procesi and the Camassa-Holm equation as an ODE on the Fr\'echet space of all smooth functions on the circle.Comment: 17 page

From Head to Hind: Elucidating Function through Contrasting Morphometrics of Ancient and Modern Pedigree Dogs.

Used together, caliper- and geometric-based morphometric analyses provide complimentary approaches to classifying form and function of archaeozoological remains. Here we apply these analytical tools to the skeletal remains of an ancient male dog unearthed from a rural farm settlement of Roman date near present day Warmington, UK. Our comparisons of the Warmington Roman dog against the morphological characteristics of modern dog breeds enabled us to establish the former's size and shape. It was of medium stature. Analysis of viscerocrania and neurocrania indicate it falls within the meso- to dolichocephalic rankings of modern dogs. The neurocranium shape and the dimensions of its long bones strongly suggest that the Warmington dog shares similarities to modern sight hounds. Historically sight hounds were bred for speed, as necessitated of a hunter that runs down small prey. Our analysis suggests that the Warmington dog was likely bred for, or derived from, Roman hunting stock. By revealing the Warmington Roman dog's form from cranial and postcranial analyses, we shed light on Roman life in one of the furthest outposts of the Roman Empire

Specific heat study of single crystalline Pr0.63_{0.63} Ca0.37_{0.37} MnO3_{3} in presence of a magnetic field

We present the results of a study of specific heat on a single crystal of Pr$_{0.63}$Ca$_{0.37}$MnO$_3$ performed over a temperature range 3K-300K in presence of 0 and 8T magnetic fields. An estimate of the entropy and latent heat in a magnetic field at the first order charge ordering (CO) transition is presented. The total entropy change at the CO transition which is $\approx$ 1.8 J/mol K at 0T, decreases to $\sim$ 1.5 J/mol K in presence of 8T magnetic field. Our measurements enable us to estimate the latent heat $L_{CO}$ $\approx$ 235 J/mol involved in the CO transition. Since the entropy of the ferromagnetic metallic (FMM) state is comparable to that of the charge-ordered insulating (COI) state, a subtle change in entropy stabilises either of these two states. Our low temperature specific heat measurements reveal that the linear term is absent in 0T and surprisingly not seen even in the metallic FMM state.Comment: 8 pages (in RevTEX format), 12 figures (in postscript format) Submitted to Phys. Rev.

Lifespan theorem for constrained surface diffusion flows

We consider closed immersed hypersurfaces in $\R^{3}$ and $\R^4$ evolving by a class of constrained surface diffusion flows. Our result, similar to earlier results for the Willmore flow, gives both a positive lower bound on the time for which a smooth solution exists, and a small upper bound on a power of the total curvature during this time. By phrasing the theorem in terms of the concentration of curvature in the initial surface, our result holds for very general initial data and has applications to further development in asymptotic analysis for these flows.Comment: 29 pages. arXiv admin note: substantial text overlap with arXiv:1201.657

Specific heat and magnetic measurements in Nd0.5Sr0.5MnO3, Nd0.5Ca0.5MnO3 and Ho0.5Ca0.5MnO3 samples

We studied the magnetization as a function of temperature and magnetic field in the compounds Nd0.5Sr0.5MnO3, Nd0.5Ca0.5MnO3 and Ho0.5Ca0.5MnO3. It allowed us to identify the ferromagnetic, antiferromagnetic and charge ordering phases in each case. The intrinsic magnetic moments of Nd3+ and Ho3+ ions experienced a short range order at low temperatures. We also did specific heat measurements with applied magnetic fields between 0 and 9 T and temperatures between 2 and 300 K in all three samples. Close to the charge ordering and ferromagnetic transition temperatures the specific heat curves showed peaks superposed to the characteristic response of the lattice oscillations. Below 10 K the specific heat measurements evidenced a Schottky-like anomaly for all samples. However, we could not successfully fit the curves to either a two level nor a distribution of two-level Schottky anomaly. Our results indicated that the peak temperature of the Schottky anomaly was higher in the compounds with narrower conduction band.Comment: submitted to PR

Competition of charge, orbital, and ferromagnetic correlations in layered manganites

The competition of charge, orbital, and ferromagnetic interactions in layered manganites is investigated by magneto-Raman scattering spectroscopy. We find that the colossal magnetoresistance effect in the layered compounds results from the interplay of the orbital and ferromagnetic double-exchange correlations. Inelastic scattering by charge-order fluctuations dominates the quasiparticle dynamics in the ferromagnetic-metal state. The scattering is suppressed at low frequencies, consistent with the opening of a charge-density wave pseudogap.Comment: 10 pages, 4 figure

Quaternion-Octonion Unitary Symmetries and Analogous Casimir Operators

An attempt has been made to investigate the global SU(2) and SU(3) unitary flavor symmetries systematically in terms of quaternion and octonion respectively. It is shown that these symmetries are suitably handled with quaternions and octonions in order to obtain their generators, commutation rules and symmetry properties. Accordingly, Casimir operators for SU(2)and SU(3) flavor symmetries are also constructed for the proper testing of these symmetries in terms of quaternions and octonions