Differential production of superoxide by neuronal mitochondria

<p>Abstract</p> <p>Background</p> <p>Mitochondrial DNA (mtDNA) mutations, which are present in all mitochondria-containing cells, paradoxically cause tissue-specific disease. For example, Leber's hereditary optic neuropathy (LHON) results from one of three point mutations mtDNA coding for complex I components, but is only manifested in retinal ganglion cells (RGCs), a central neuron contained within the retina. Given that RGCs use superoxide for intracellular signaling after axotomy, and that LHON mutations increase superoxide levels in non-RGC transmitochondrial cybrids, we hypothesized that RGCs regulate superoxide levels differently than other neuronal cells. To study this, we compared superoxide production and mitochondrial electron transport chain (METC) components in isolated RGC mitochondria to mitochondria isolated from cerebral cortex and neuroblastoma SK-N-AS cells.</p> <p>Results</p> <p>In the presence of the complex I substrate glutamate/malate or the complex II substrate succinate, the rate of superoxide production in RGC-5 cells was significantly lower than cerebral or neuroblastoma cells. Cerebral but not RGC-5 or neuroblastoma cells increased superoxide production in response to the complex I inhibitor rotenone, while neuroblastoma but not cerebral or RGC-5 cells dramatically decreased superoxide production in response to the complex III inhibitor antimycin A. Immunoblotting and real-time quantitative PCR of METC components demonstrated different patterns of expression among the three different sources of neuronal mitochondria.</p> <p>Conclusion</p> <p>RGC-5 mitochondria produce superoxide at significantly lower rates than cerebral and neuroblastoma mitochondria, most likely as a result of differential expression of complex I components. Diversity in METC component expression and function could explain tissue specificity in diseases associated with inherited mtDNA abnormalities.</p

Saharan dust and ice nuclei over Central Europe

Surface measurements of aerosol and ice nuclei (IN) at a Central European mountain site during an episode of dust transport from the Sahara are presented. Ice nuclei were sampled by electrostatic precipitation on silicon wafers and were analyzed in an isothermal static vapor diffusion chamber. The transport of mineral dust is simulated by the Eulerian regional dust model DREAM. Ice nuclei and mineral dust are significantly correlated, in particular IN number concentration and aerosol surface area. The ice nucleating characteristics of the aerosol as analyzed with respect to temperature and supersaturation are similar during the dust episode than during the course of the year. This suggests that dust may be a main constituent of ice nucleating aerosols in Central Europe

Laser-Based Single-Axon Transection for High-Content Axon Injury and Regeneration Studies

The investigation of the regenerative response of the neurons to axonal injury is essential to the development of new axoprotective therapies. Here we study the retinal neuronal RGC-5 cell line after laser transection, demonstrating that the ability of these cells to initiate a regenerative response correlates with axon length and cell motility after injury. We show that low energy picosecond laser pulses can achieve transection of unlabeled single axons in vitro and precisely induce damage with micron precision. We established the conditions to achieve axon transection, and characterized RGC-5 axon regeneration and cell body response using time-lapse microscopy. We developed an algorithm to analyze cell trajectories and established correlations between cell motility after injury, axon length, and the initiation of the regeneration response. The characterization of the motile response of axotomized RGC-5 cells showed that cells that were capable of repair or regrowth of damaged axons migrated more slowly than cells that could not. Moreover, we established that RGC-5 cells with long axons could not recover their injured axons, and such cells were much more motile. The platform we describe allows highly controlled axonal damage with subcellular resolution and the performance of high-content screening in cell cultures

The karabus affair speaks to larger issues for american academic and medical centers.

Finally, on March 12, 2013, a major American newspaper, The Wall Street Journal, reported on the plight of Dr. Cyril Karabus (1,2). Dr. Karabus is the 78 year old pediatric oncologist from Claremont, Capetown, South Africa who is well known as the retired head of the Oncology and Hematology Unit of the Red Cross Children’s Hospital, University of Cape Town, as well as for his devoted service to poor children in the apartheid era. In 2002, he cared for a three-year old Yemeni girl with acute myelogenous leukemia during a locum tenens in the United Arab Emirates (UAE)

The antisaccade task as an index of sustained goal activation in working memory: modulation by nicotine

The antisaccade task provides a laboratory analogue of situations in which execution of the correct behavioural response requires the suppression of a more prepotent or habitual response. Errors (failures to inhibit a reflexive prosaccade towards a sudden onset target) are significantly increased in patients with damage to the dorsolateral prefrontal cortex and patients with schizophrenia. Recent models of antisaccade performance suggest that errors are more likely to occur when the intention to initiate an antisaccade is insufficiently activated within working memory. Nicotine has been shown to enhance specific working memory processes in healthy adults. MATERIALS AND METHODS: We explored the effect of nicotine on antisaccade performance in a large sample (N = 44) of young adult smokers. Minimally abstinent participants attended two test sessions and were asked to smoke one of their own cigarettes between baseline and retest during one session only. RESULTS AND CONCLUSION: Nicotine reduced antisaccade errors and correct antisaccade latencies if delivered before optimum performance levels are achieved, suggesting that nicotine supports the activation of intentions in working memory during task performance. The implications of this research for current theoretical accounts of antisaccade performance, and for interpreting the increased rate of antisaccade errors found in some psychiatric patient groups are discussed

The nuclear star cluster of the Milky Way: proper motions and mass

Nuclear star clusters (NSCs) are located at the photometric and dynamical centers of the majority of galaxies. They are among the densest star clusters in the Universe. The NSC in the Milky Way is the only object of this class that can be resolved into individual stars. We measured the proper motions of more than 6000 stars within ~1.0 pc of the supermassive black hole Sgr A*. The full data set is provided in this work. We largely exclude the known early-type stars with their peculiar dynamical properties from the dynamical analysis. The cluster is found to rotate parallel to Galactic rotation, while the velocity dispersion appears isotropic (or anisotropy may be masked by the cluster rotation). The Keplerian fall-off of the velocity dispersion due to the point mass of Sgr A* is clearly detectable only at R <~ 0.3 pc. Nonparametric isotropic and anisotropic Jeans models are applied to the data. They imply a best-fit black hole mass of 3.6 (+0.2/-0.4) x 10^6 solar masses. Although this value is slightly lower than the current canonical value of 4.0x10^6 solar masses, this is the first time that a proper motion analysis provides a mass for Sagittarius A* that is consistent with the mass inferred from orbits of individual stars. The point mass of Sagittarius A* is not sufficient to explain the velocity data. In addition to the black hole, the models require the presence of an extended mass of 0.5-1.5x10^6 solar masses in the central parsec. This is the first time that the extended mass of the nuclear star cluster is unambiguously detected. The influence of the extended mass on the gravitational potential becomes notable at distances >~0.4 pc from Sgr A*. Constraints on the distribution of this extended mass are weak. The extended mass can be explained well by the mass of the stars that make up the cluster.Comment: accepted for publication in Astronomy & Astrophysics; please contact first author for higher quality figure