Angiotensin-(1-7) receptor Mas deficiency does not exacerbate cardiac atrophy following high-level spinal cord injury in mice

Experimental spinal cord injury (SCI) causes a morphological and functional deterioration of the heart, in which the renin–angiotensin system (RAS) might play a role. The recently discovered non-canonical axis of RAS with angiotensin-(1-7) and its receptor Mas, which is associated with cardioprotection could be essential to prevent damage to the heart following SCI. We investigated the cardiac consequences of SCI and the role of Mas in female wild-type (WT, n = 22) and mice deficient of Mas (Mas(-/-), n = 25) which underwent spinal cord transection at thoracic level T4 (T4-Tx) or sham-operation by echocardiography (0, 7, 21, and 28 days post-SCI), histology and gene expression analysis at 1 or 2 months post-SCI. We found left ventricular mass reduction with preserved ejection fraction (EF) and fractional shortening in WT as well as Mas(-/-) mice. Cardiac output was reduced in Mas(-/-) mice, whereas stroke volume (SV) was reduced in WT T4-Tx mice. Echocardiographic indices did not differ between the genotypes. Smaller heart weight (HW) and smaller cardiomyocyte diameter at 1 month post-SCI compared to sham mice was independent of genotype. The muscle-specific E3 ubiquitin ligases Atrogin-1/MAFbx and MuRF1 were upregulated or showed a trend for upregulation in WT mice at 2 months post-SCI, respectively. Angiotensinogen gene expression was upregulated at 1 month post-SCI and angiotensin II receptor type 2 downregulated at 2 month post-SCI in Mas(-/-) mice. Mas was downregulated post-SCI. Cardiac atrophy following SCI, not exacerbated by lack of Mas, is a physiological reaction as there were no signs of cardiac pathology and dysfunction

Berichte

Michael SchmolkeHenk Prakke 90 Jahre altElisabeth RosenmayrKonferenz der europäischen Medienbischöfe22.-25. März 1990 in Fatima (Portugal) Alexander S. ScottiSolidarnosc-Filmstudio Danzi

Angiotensin‐II receptor type Ia does not contribute to cardiac atrophy following high‐thoracic spinal cord injury in mice

NEW FINDINGS: What is the central question of this study? Spinal cord injury leads to cardiac atrophy and the role of the renin-angiotensin system with angiotensin II acting via its receptor AT1a in this effect has not been previously explored. What is the main finding and its importance? In mice undergone thoracic level 4 transection, we confirm cardiac atrophy. Knockout of AT1a does not protect mice from cardiac atrophy. We observed no histopathological signs but reduced load-dependent left ventricular function (lower stroke volume and cardiac output) with preserved ejection fraction. Further investigations are warranted to assess cardiac function under stress conditions. ABSTRACT: Spinal cord injury (SCI) leads to cardiac atrophy often accompanied by functional deficits. The renin-angiotensin system (RAS) with angiotensin II (AngII) signalling via its receptor AT1a might contribute to cardiac atrophy post-SCI. We performed spinal cord transection at thoracic level T4 (T4-Tx) or sham-operation in female wild type mice (WT, n = 27) and mice deficient of AT1a (Agtr1a(-/-), n = 27). Echocardiography (0, 7, 21 and 28 days post-SCI) as well as histology and gene expression analyses at 1 and 2 months post-SCI were performed. We found cardiac atrophy post-SCI: reduced heart weight, estimated left ventricular mass in Agtr1a(-/-), and cardiomyocyte diameter in WT mice. Although, the latter as well as stroke volume (SV) and cardiac output (CO) were reduced in Agtr1a(-/-) mice already at baseline, cardiomyocyte diameter was even smaller in injured Agtr1a(-/-) mice compared to injured WT mice. SV and CO were reduced in WT mice post-SCI. Ejection fraction and fractional shortening was preserved post-SCI in both genotypes. There were no histological signs of fibrosis and pathology in the cardiac sections of both genotypes post-SCI. Gene expression of Agtr1a showed a trend for upregulation at 2 months post-SCI, angiotensinogen was upregulated at 2 month post-SCI in both genotypes. AngII receptor type 2 (Agtr2) was up-and down-regulated at 1 and 2 months post-SCI in WT mice, respectively, and Ang-(1-7) receptor (Mas) at 1 and 2 months post-SCI. Atrogin-1/MAFbx and MuRF1, the atrophy markers were not significantly upregulated post-SCI. Our data shows that lack of AT1a does not protect from cardiac atrophy post-SCI

Scaling of the specific heat in superfluid films

We study the specific heat of the $x-y$ model on lattices $L \times L \times H$ with $L \gg H$ (i.e. on lattices representing a film geometry) using the Cluster Monte--Carlo method. In the $H$--direction we apply Dirichlet boundary conditions so that the order parameter in the top and bottom layers is zero. We find that our results for the specific heat of various thickness size $H$ collapse on the same universal scaling function. The extracted scaling function of the specific heat is in good agreement with the experimentally determined universal scaling function using no free parameters.Comment: 4 pages, uuencoded compressed PostScrip

Scaling of thermal conductivity of helium confined in pores

We have studied the thermal conductivity of confined superfluids on a bar-like geometry. We use the planar magnet lattice model on a lattice $H\times H\times L$ with $L \gg H$. We have applied open boundary conditions on the bar sides (the confined directions of length $H$) and periodic along the long direction. We have adopted a hybrid Monte Carlo algorithm to efficiently deal with the critical slowing down and in order to solve the dynamical equations of motion we use a discretization technique which introduces errors only $O((\delta t)^6)$ in the time step $\delta t$. Our results demonstrate the validity of scaling using known values of the critical exponents and we obtained the scaling function of the thermal resistivity. We find that our results for the thermal resistivity scaling function are in very good agreement with the available experimental results for pores using the tempComment: 5 two-column pages, 3 figures, Revtex

DNA immunization as a technology platform for monoclonal antibody induction

To combat the threat of many emerging infectious diseases, DNA immunization offers a unique and powerful approach to the production of high-quality monoclonal antibodies (mAbs) against various pathogens. Compared with traditional protein-based immunization approaches, DNA immunization is efficient for testing novel immunogen designs, does not require the production or purification of proteins from a pathogen or the use of recombinant protein technology and is effective at generating mAbs against conformation-sensitive targets. Although significant progress in the use of DNA immunization to generate mAbs has been made over the last two decades, the literature does not contain an updated summary of this experience. The current review provides a comprehensive analysis of the literature, including our own work, describing the use of DNA immunization to produce highly functional mAbs, in particular, those against emerging infectious diseases. Critical factors such as immunogen design, delivery approach, immunization schedule, use of immune modulators and the role of final boost immunization are discussed in detail

Perturbative calculation of the scaled factorial moments in second-order quark-hadron phase transition within the Ginzburg-Landau description

The scaled factorial moments $F_q$ are studied for a second-order quark-hadron phase transition within the Ginzburg-Landau description. The role played by the ground state of the system under low temperature is emphasized. After a local shift of the order parameter the fluctuations are around the ground state, and a perturbative calculation for $F_q$ can be carried out. Power scaling between $F_q$'s is shown, and a universal scaling exponent $\nu\simeq 1.75$ is given for the case with weak correlations and weak self-interactions.Comment: 12 pages in RevTeX, 12 eps figure

Li14Ln5[Si11N19O5]O2F2 with Ln = Ce, Nd-Representatives of a Family of Potential Lithium Ion Conductors

The isotypic layered oxonitridosilicates Li14Ln5[Si11N19O5]O2F2 (Ln = Ce, Nd) have been synthesized using Li as fluxing agent and crystallize in the orthorhombic space group Pmmn (Z = 2, Li14Ce5[Si11N19O5]O2F2: a = 17.178(3), b = 7.6500(15), c = 10.116(2) Å, R1 = 0.0409, wR2 = 0.0896; Li14Nd5 Si11N19O5]O2F2: a = 17.126(2), b = 7.6155 15), c = 10.123(2) Å, R1 = 0.0419, wR2 = 0.0929). The silicate layers consist of dreier and sechser rings interconnected via common corners, yielding an unprecedented silicate substructure. A topostructural analysis indicates possible 1D ion migration pathways between five crystallographic independent Li positions. The specific Li-ionic conductivity and its temperature dependence were determined by impedance spectroscopy as well as DC polarization/depolarization measurements. The ionic conductivity is on the order of 5 × 10−5 S/cm at 300°C, while the activation energy is 0.69 eV. Further adjustments of the defect chemistry (e.g., through doping)can make these compounds interesting candidates for novel oxonitridosilicate based ion conductors