Regulation of renin gene expression in kidneys of eNOS- and nNOS-deficient mice

Our study aimed to assess the roles of nitric oxide derived from endothelium NO-synthase (eNOS) and macula densa neuronal NO-synthase (nNOS) in the regulation of renal renin expression. For this purpose renin mRNA levels and renin content were determined in kidneys of wild-type (wt), nNOS-deficient (nNOS–/–), and eNOS-deficient (eNOS–/–) mice, in which the renin system was suppressed by feeding a high-salt diet (NaCl 4%), or was stimulated by feeding a low-salt (NaCl 0.02%) diet together with the converting-enzyme inhibitor ramipril (10 mg kg –1 day –1 ). In all mouse strains, renin mRNA levels were inversely related to the rate of sodium intake. In eNOS–/– mice renin mRNA levels and renal renin content were 50% lower than in wt mice at each level of salt intake, whilst in nNOS–/– mice renin expression was not different from wt controls. Administration of the general NO-synthase inhibitor nitro- l -arginine methyl ester ( l -NAME, 50 mg kg –1 day –1 ) to mice kept on the low-salt/ramipril regimen caused a decrease of renal renin mRNA levels in wt and nNOS–/– mice, but not in eNOS–/– mice. These observations suggest that neither eNOS nor nNOS is essential for up- or downregulation of renin expression. eNOS-derived NO appears to enhance renin expression, whereas nNOS-derived NO does not.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42244/1/424-439-5-567_s004249900214.pd

Formation of a stable deacagonal quasicrystalline Al-Pd-Mn surface layer

We report the in situ formation of an ordered equilibrium decagonal Al-Pd-Mn quasicrystal overlayer on the 5-fold symmetric surface of an icosahedral Al-Pd-Mn monograin. The decagonal structure of the epilayer is evidenced by x-ray photoelectron diffraction, low-energy electron diffraction and electron backscatter diffraction. This overlayer is also characterized by a reduced density of states near the Fermi edge as expected for quasicrystals. This is the first time that a millimeter-size surface of the stable decagonal Al-Pd-Mn is obtained, studied and compared to its icosahedral counterpart.Comment: Submitted to Phys. Ref. Lett. (18 July 2001

Anomalous yielding in the complex metallic alloy Al13Co4

The single crystal deformation behaviour of orthorhombic Al13Co4 hasbeen studied below the brittle-ductile transition temperature observedin bulk material from room temperature to 600 degrees C, usingindentation, microcompression and transmission electron microscopy. Atroom temperature, slip occurred most easily by dislocation motion on the(0 0 1)[0 1 0] slip system, as observed in the ductile regime at hightemperatures. However, as the temperature was increased towards 600degrees C, the slip pattern changed to one consisting of linear defectsrunning perpendicular to the loading axis. Serrated flow was observed atall temperatures, although at 600 degrees C the magnitude of theserrations decreased. Anomalous yielding behaviour was also observedabove 226 degrees C, where both the yield and the 2\% flow stressincreased with temperature, almost doubling between 226 and 600 degreesC. It has been suggested that this might arise due to the increasingstability of orthorhombic Al13Co4 with respect to the monoclinic formwith increasing temperature. This is shown to be consistent with thetheoretical predictions that exist

OXPHOS Supercomplexes as a Hallmark of the Mitochondrial Phenotype of Adipogenic Differentiated Human MSCs

Mitochondria are essential organelles with multiple functions, especially in energy metabolism. Recently, an increasing number of data has highlighted the role of mitochondria for cellular differentiation processes. Metabolic differences between stem cells and mature derivatives require an adaptation of mitochondrial function during differentiation. In this study we investigated alterations of the mitochondrial phenotype of human mesenchymal stem cells undergoing adipogenic differentiation. Maturation of adipocytes is accompanied by mitochondrial biogenesis and an increase of oxidative metabolism. Adaptation of the mt phenotype during differentiation is reflected by changes in the distribution of the mitochondrial network as well as marked alterations of gene expression and organization of the oxidative phosphorylation system (OXPHOS). Distinct differences in the supramolecular organization forms of cytochrome c oxidase (COX) were detected using 2D blue native (BN)-PAGE analysis. Most remarkably we observed a significant increase in the abundance of OXPHOS supercomplexes in mitochondria, emphasizing the change of the mitochondrial phenotype during adipogenic differentiation

Odorant-Dependent Generation of Nitric Oxide in Mammalian Olfactory Sensory Neurons

The gaseous signalling molecule nitric oxide (NO) is involved in various physiological processes including regulation of blood pressure, immunocytotoxicity and neurotransmission. In the mammalian olfactory bulb (OB), NO plays a role in the formation of olfactory memory evoked by pheromones as well as conventional odorants. While NO generated by the neuronal isoform of NO synthase (nNOS) regulates neurogenesis in the olfactory epithelium, NO has not been implicated in olfactory signal transduction. We now show the expression and function of the endothelial isoform of NO synthase (eNOS) in mature olfactory sensory neurons (OSNs) of adult mice. Using NO-sensitive micro electrodes, we show that stimulation liberates NO from isolated wild-type OSNs, but not from OSNs of eNOS deficient mice. Integrated electrophysiological recordings (electro-olfactograms or EOGs) from the olfactory epithelium of these mice show that NO plays a significant role in modulating adaptation. Evidence for the presence of eNOS in mature mammalian OSNs and its involvement in odorant adaptation implicates NO as an important new element involved in olfactory signal transduction. As a diffusible messenger, NO could also have additional functions related to cross adaptation, regeneration, and maintenance of MOE homeostasis

Endogenous myoglobin in human breast cancer is a hallmark of luminal cancer phenotype

BACKGROUND: We aimed to clarify the incidence and the clinicopathological value of non-muscle myoglobin (Mb) in a large cohort of non-invasive and invasive breast cancer cases. METHODS: Matched pairs of breast tissues from 10 patients plus 17 breast cell lines were screened by quantitative PCR for Mb mRNA. In addition, 917 invasive and 155 non-invasive breast cancer cases were analysed by immunohistochemistry for Mb expression and correlated to clinicopathological parameters and basal molecular characteristics including oestrogen receptor-alpha (ERalpha)/progesteron receptor (PR)/HER2, fatty acid synthase (FASN), hypoxia-inducible factor-1alpha (HIF-1alpha), HIF-2alpha, glucose transporter 1 (GLUT1) and carbonic anhydrase IX (CAIX). The spatial relationship of Mb and ERalpha or FASN was followed up by double immunofluorescence. Finally, the effects of estradiol treatment and FASN inhibition on Mb expression in breast cancer cells were analysed. RESULTS: Myoglobin mRNA was found in a subset of breast cancer cell lines; in microdissected tumours Mb transcript was markedly upregulated. In all, 71% of tumours displayed Mb protein expression in significant correlation with a positive hormone receptor status and better prognosis. In silico data mining confirmed higher Mb levels in luminal-type breast cancer. Myoglobin was also correlated to FASN, HIF-2alpha and CAIX, but not to HIF-1alpha or GLUT1, suggesting hypoxia to participate in its regulation. Double immunofluorescence showed a cellular co-expression of ERalpha or FASN and Mb. In addition, Mb levels were modulated on estradiol treatment and FASN inhibition in a cell model. CONCLUSION: We conclude that in breast cancer, Mb is co-expressed with ERalpha and co-regulated by oestrogen signalling and can be considered a hallmark of luminal breast cancer phenotype. This and its possible new role in fatty acid metabolism may have fundamental implications for our understanding of Mb in solid tumours

Neural network model of the primary visual cortex: From functional architecture to lateral connectivity and back

The role of intrinsic cortical dynamics is a debatable issue. A recent optical imaging study (Kenet et al., 2003) found that activity patterns similar to orientation maps (OMs), emerge in the primary visual cortex (V1) even in the absence of sensory input, suggesting an intrinsic mechanism of OM activation. To better understand these results and shed light on the intrinsic V1 processing, we suggest a neural network model in which OMs are encoded by the intrinsic lateral connections. The proposed connectivity pattern depends on the preferred orientation and, unlike previous models, on the degree of orientation selectivity of the interconnected neurons. We prove that the network has a ring attractor composed of an approximated version of the OMs. Consequently, OMs emerge spontaneously when the network is presented with an unstructured noisy input. Simulations show that the model can be applied to experimental data and generate realistic OMs. We study a variation of the model with spatially restricted connections, and show that it gives rise to states composed of several OMs. We hypothesize that these states can represent local properties of the visual scene

Abstracts from the 8th International Conference on cGMP Generators, Effectors and Therapeutic Implications

This work was supported by a restricted research grant of Bayer AG