Structural and paramagnetic properties of dilute Ga1-xMnxN

Systematic investigations of the structural and magnetic properties of single crystal (Ga,Mn)N films grown by metal organic vapor phase epitaxy are presented. High resolution transmission electron microscopy, synchrotron x-ray diffraction, and extended x-ray absorption fine structure studies do not reveal any crystallographic phase separation and indicate that Mn occupies Ga-substitutional sites in the Mn concentration range up to 1%. The magnetic properties as a function of temperature, magnetic field and its orientation with respect to the c-axis of the wurtzite structure can be quantitatively described by the paramagnetic theory of an ensemble of non-interacting Mn$^{3+}$ ions in the relevant crystal field, a conclusion consistent with the x-ray absorption near edge structure analysis. A negligible contribution of Mn in the 2+ charge state points to a low concentration of residual donors in the studied films. Studies on modulation doped p-type (Ga,Mn)N/(Ga,Al)N:Mg heterostructures do not reproduce the high temperature robust ferromagnetism reported recently for this system.Comment: 15 pages, 14 figure

Combined Inhibition of the Renin-Angiotensin System and Neprilysin Positively Influences Complex Mitochondrial Adaptations in Progressive Experimental Heart Failure.

BACKGROUND:Inhibitors of the renin angiotensin system and neprilysin (RAS-/NEP-inhibitors) proved to be extraordinarily beneficial in systolic heart failure. Furthermore, compelling evidence exists that impaired mitochondrial pathways are causatively involved in progressive left ventricular (LV) dysfunction. Consequently, we aimed to assess whether RAS-/NEP-inhibition can attenuate mitochondrial adaptations in experimental heart failure (HF). METHODS AND RESULTS:By progressive right ventricular pacing, distinct HF stages were induced in 15 rabbits, and 6 animals served as controls (CTRL). Six animals with manifest HF (CHF) were treated with the RAS-/NEP-inhibitor omapatrilat. Echocardiographic studies and invasive blood pressure measurements were undertaken during HF progression. Mitochondria were isolated from LV tissue, respectively, and further worked up for proteomic analysis using the SWATH technique. Enzymatic activities of citrate synthase and the electron transfer chain (ETC) complexes I, II, and IV were assessed. Ultrastructural analyses were performed by transmission electron microscopy. During progression to overt HF, intricate expression changes were mainly detected for proteins belonging to the tricarboxylic acid cycle, glucose and fat metabolism, and the ETC complexes, even though ETC complex I, II, or IV enzymatic activities were not significantly influenced. Treatment with a RAS-/NEP-inhibitor then reversed some maladaptive metabolic adaptations, positively influenced the decline of citrate synthase activity, and altered the composition of each respiratory chain complex, even though this was again not accompanied by altered ETC complex enzymatic activities. Finally, ultrastructural evidence pointed to a reduction of autophagolytic and degenerative processes with omapatrilat-treatment. CONCLUSIONS:This study describes complex adaptations of the mitochondrial proteome in experimental tachycardia-induced heart failure and shows that a combined RAS-/NEP-inhibition can beneficially influence mitochondrial key pathways

Synopsis of qualitative and quantitative proteomic results.

<p>Each color represents comparisons between two groups: gray, CTRL vs. ELVD; blue, CTRL vs. CHF; green, ELVD vs. CHF; orange, CHF vs. CHF+VPI. Data are categorized by functional assignment of the proteins to 5 classes: proteins belonging to the respiratory chain, metabolism, fat metabolism, cellular structure, and ribosomes. Each bar in the upper part of the figure represents one differently expressed protein with its fold change, respectively. Colored circles in the lower part of the figure each indicate the mean value of fold changes with the size of circles representing the number of differentially expressed proteins. The colours of the circles again reflect the comparison groups as detailed above. “Metabolism” comprises proteins with metabolic properties except for the ones belonging to “fat metabolism”.</p

Transmission electron microscopy.

<p>By comparing CHF with CHF-VPI, differences were seen regarding myelin-like figures, paracrystalline structures, and lipid droplets. Plus signs represent the results of semiquantitative analyses.</p

Protein expression level of carnitine palmitoyltransferase 1 A normalized to the expression of the outer mitochondrial membrane protein VDAC.

<p>Protein expression level of carnitine palmitoyltransferase 1 A normalized to the expression of the outer mitochondrial membrane protein VDAC.</p

Synopsis of different pathway regulation patterns.

<p>Synopsis of different pathway regulation patterns.</p

Enzymatic activity of succinate dehydrogenase (ETC complex II).

<p>Enzymatic activity of succinate dehydrogenase (ETC complex II).</p

Enzymatic activity of NADH dehydrogenase (ETC complex I).

<p>Enzymatic activity of NADH dehydrogenase (ETC complex I).</p