Histopathologic Evolution of Cardiomyopathy in a Canine Model of Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is a recessive X-linked disorder characterized for mutation in dystrophin gene and manifested by progressive degeneration and necrosis of skeletal and cardiac muscle with replacement leading to generalized muscular weakness and atrophy. The dog Golden Retriever Muscular Dystrophy (GRMD) is the best experimental model for DMD, with genotypic and phenotypic manifestations closely of human disease. Similar to patients with DMD, heart failure is a major cause of death in GRMD animals. The objective of this study was to evaluate the pathological progression of myocardial lesions from GRMD dogs in different ages in order to clarify the pathogenesis of Duchenne´s cardiomyopathy. Fragments of left and right ventricle and interventricular septum, from 18 GRMD dogs between 6 to 51 months were collected, fixed, dehydrated, clarified, and finally embedded in paraffin. Five micrometer thick serial sections were obtained and stained with Hematoxylin-Eosin (HE), Picrosirius red, and Von Kossa. Histological analyses were performed at the light microscopy. Myocardial lesions were observed in all GRMD dogs and the sequence of cardiac lesion classified according to according to the age included: abnormal calcium accumulation, myofibrillar necrosis, proliferation of granulation tissue, endomysial and perimysial fibrosis, and finally myocardial fatty infiltration. Interestingly, several Anitschkow cells, the hallmark of rheumatic carditis, were detected in inflammatory infiltrate present at granulation tissue. Our results demonstrate the sequence of cardiac lesions that determine the cardiomyopathy in Golden Retriever dogs affected by DMD and exhibit, for the first time, the Anitschkow cells in the histological findings of this cardiomyopathy. These results are relevant for to clarify the pathogenesis of cardiomyopathy in dogs and humans affected by DMD

Combining M-FISH and Quantum Dot technology for fast chromosomal assignment of transgenic insertions

<p>Abstract</p> <p>Background</p> <p>Physical mapping of transgenic insertions by Fluorescence in situ Hybridization (FISH) is a reliable and cost-effective technique. Chromosomal assignment is commonly achieved either by concurrent G-banding or by a multi-color FISH approach consisting of iteratively co-hybridizing the transgenic sequence of interest with one or more chromosome-specific probes at a time, until the location of the transgenic insertion is identified.</p> <p>Results</p> <p>Here we report a technical development for fast chromosomal assignment of transgenic insertions at the single cell level in mouse and rat models. This comprises a simplified 'single denaturation mixed hybridization' procedure that combines multi-color karyotyping by Multiplex FISH (M-FISH), for simultaneous and unambiguous identification of all chromosomes at once, and the use of a Quantum Dot (QD) conjugate for the transgene detection.</p> <p>Conclusions</p> <p>Although the exploitation of the unique optical properties of QD nanocrystals, such as photo-stability and brightness, to improve FISH performance generally has been previously investigated, to our knowledge this is the first report of a purpose-designed molecular cytogenetic protocol in which the combined use of QDs and standard organic fluorophores is specifically tailored to assist gene transfer technology.</p

Using polyacrilamide with sprinkler irrigation to improve infiltration

ABSTRACT: Center-pivot irrigation systems often apply water at rates greater than the soil infiltration rate. Applying high molecular weight, water-soluble, anionic polyacrylamide (PAM) to the soil can improve infiltration and reduce soil erosion The objective of this study was to determine whether single and multiple PAM applications with sprinkler irrigation improved infiltration under field conditions. A two-year study conducted near Kimberly, Idaho, used a solid-set sprinkler system, and a one-year study conducted in Monte dos Alhos near Alvalade do Sado, Portugal, used a center pivot. At Kimberly, applying PAM with four irrigations (total applied PAM was 2.1 kg ha−1 in 2000 and 3.0 kg ha−1 in 2001) significantly reduced total measured runoff, from 5.9 mm (2000) and 9.2 mm (2001) for the control to 2.0 and 2.1 mm. Total measured soil erosion was also reduced from 52 and 34 kg ha−1 for the control to 21 and 5 kg ha−1 for the multiple PAM treatment. Applying similar or greater amounts of PAM with a single irrigation reduced erosion, but not runoff, compared with the control. In the Monte dos Alhos study, runoff was reduced by applying a total of 0.3 kg PAM ha−1 with a single irrigation (43 mm runoff) or three irrigations (65 mm runoff) compared with the control (111 mm runoff). Measured soil erosion was not significantly different among treatments. Applying PAM with multiple irrigations extended its effectiveness as long as the application rate was great enough to adequately stabilize the soil surface during the first irrigation

Geodesic distance for right invariant Sobolev metrics of fractional order on the diffeomorphism group

We study Sobolev-type metrics of fractional order $s\geq0$ on the group \Diff_c(M) of compactly supported diffeomorphisms of a manifold $M$. We show that for the important special case $M=S^1$ the geodesic distance on \Diff_c(S^1) vanishes if and only if $s\leq\frac12$. For other manifolds we obtain a partial characterization: the geodesic distance on \Diff_c(M) vanishes for $M=\R\times N, s<\frac12$ and for $M=S^1\times N, s\leq\frac12$, with $N$ being a compact Riemannian manifold. On the other hand the geodesic distance on \Diff_c(M) is positive for $\dim(M)=1, s>\frac12$ and $\dim(M)\geq2, s\geq1$. For $M=\R^n$ we discuss the geodesic equations for these metrics. For $n=1$ we obtain some well known PDEs of hydrodynamics: Burgers' equation for $s=0$, the modified Constantin-Lax-Majda equation for $s=\frac 12$ and the Camassa-Holm equation for $s=1$.Comment: 16 pages. Final versio

Risks, alternative knowledge strategies and democratic legitimacy: the conflict over co-incineration of hazardous industrial waste in Portugal.

The decision to incinerate hazardous industrial waste in cement plants (the socalled ‘co-incineration’ process) gave rise to one of the most heated environmental conflicts ever to take place in Portugal. The bitterest period was between 1997 and 2002, after the government had made a decision. Strong protests by residents, environmental organizations, opposition parties, and some members of the scientific community forced the government to backtrack and to seek scientific legitimacy for the process through scientific expertise. The experts ratified the government’s decision, stating that the risks involved were socially acceptable. The conflict persisted over a decade and ended up clearing the way for a more sustainable method over which there was broad social consensus – a multifunctional method which makes it possible to treat, recover and regenerate most wastes. Focusing the analysis on this conflict, this paper has three aims: (1) to discuss the implications of the fact that expertise was ‘confiscated’ after the government had committed itself to the decision to implement co-incineration and by way of a reaction to the atmosphere of tension and protest; (2) to analyse the uses of the notions of ‘risk’ and ‘uncertainty’ in scientific reports from both experts and counter-experts’ committees, and their different assumptions about controllability and criteria for considering certain practices to be sufficiently safe for the public; and (3) to show how the existence of different technical scientific and political attitudes (one more closely tied to government and the corporate interests of the cement plants, the other closer to the environmental values of reuse and recycling and respect for the risk perception of residents who challenged the facilities) is closely bound up with problems of democratic legitimacy. This conflict showed how adopting more sustainable and lower-risk policies implies a broader view of democratic legitimacy, one which involves both civic movements and citizens themselves

Using polyacrylamide with sprinkler irrigation to improve infiltration

Center-pivot irrigation systems often apply water at rates greater than the soil infiltration rate. Applying high molecular weight, water-soluble, anionic polyacrylamide (PAM) to the soil can improve infiltration and reduce soil erosion The objective of this study was to determine whether single and multiple PAM applications with sprinkler irrigation improved infiltration under field conditions. A two-year study conducted near Kimberly, Idaho, used a solid-set sprinkler system, and a one-year study conducted in Monte dos Alhos near Alvalade do Sado, Portugal, used a center pivot. At Kimberly, applying PAM with four irrigations (total applied PAM was 2.1 kg ha-1 in 2000 and 3.0 kg ha-1 in 2001) significantly reduced total measured runoff, from 5.9 mm (2000) and 9.2 mm (2001) for the control to 2.0 and 2.1 mm. Total measured soil erosion was also reduced from 52 and 34 kg ha 1 for the control to 21 and 5 kg ha 1 for the multiple PAM treatment. Applying similar or greater amounts of PAM with a single irrigation reduced erosion, but not runoff, compared with the control. In the Monte dos Alhos study, runoff was reduced by applying a total of 0.3 kg PAM ha 1 with a single irrigation (43 mm runoff) or three irrigations (65 mm runoff) compared with the control (111 mm runoff). Measured soil erosion was not significantly different among treatments. Applying PAM with multiple irrigations extended its effectiveness as long as the application rate was great enough to adequately stabilize the soil surface during the first irrigation

Computing the first eigenpair of the p-Laplacian via inverse iteration of sublinear supersolutions

We introduce an iterative method for computing the first eigenpair $(\lambda_{p},e_{p})$ for the $p$-Laplacian operator with homogeneous Dirichlet data as the limit of $(\mu_{q,}u_{q})$ as $q\rightarrow p^{-}$, where $u_{q}$ is the positive solution of the sublinear Lane-Emden equation $-\Delta_{p}u_{q}=\mu_{q}u_{q}^{q-1}$ with same boundary data. The method is shown to work for any smooth, bounded domain. Solutions to the Lane-Emden problem are obtained through inverse iteration of a super-solution which is derived from the solution to the torsional creep problem. Convergence of $u_{q}$ to $e_{p}$ is in the $C^{1}$-norm and the rate of convergence of $\mu_{q}$ to $\lambda_{p}$ is at least $O(p-q)$. Numerical evidence is presented.Comment: Section 5 was rewritten. Jed Brown was added as autho

Revival of the spin-Peierls transition in Cu_xZn_(1-x)GeO_3 under pressure

Pressure and temperature dependent susceptibility and Raman scattering experiments on single crystalline Cu_xZn_(1-x)GeO_3 have shown an unusually strong increase of the spin-Peierls phase transition temperature upon applying hydrostatic pressure. The large positive pressure coefficient (7.5 K/GPa) - almost twice as large as for the pure compound (4.5 K/GPa) - is interpreted as arising due to an increasing magnetic frustration which decreases the spin-spin correlation length, and thereby weakens the influence of the non-magnetic Zn-substitution.Comment: LaTeX, 15 pages, 5 eps figures, Phys. Rev. B, to appea