Monoamine oxidase-A modulates apoptotic cell death induced by staurosporine in human neuroblastoma cells

Monoamine oxidases (MAOs) are mitochondrial enzymes which control the levels of neurotransmitters in the brain and dietary amines in peripheral tissues via oxidative deamination. MAO has also been implicated in cell signalling. In this study, we describe the MAO-A isoform as functional in apoptosis induced by staurosporine (STS) in human dopaminergic neuroblastoma cells (SH-SY5Y). Increased levels of MAO-A activity were induced by STS, accompanied by increased MAO-A protein and activation of the initiator of the intrinsic pathway, caspase 9, and the executioner caspase 3. MAO-A mRNA levels were unaffected by STS, suggesting that changes in MAO-A protein are due to post-transcriptional events. Two unrelated MAO-A inhibitors reduced caspase activation. STS treatment resulted in sustained activation of the mitogen-activated protein kinase pathway enzymes extracellular regulated kinase, c-jun terminal kinase and p38, and depletion of the anti-apoptotic protein Bcl-2. These changes were significantly reversed by MAO inhibition. Production of reactive oxygen species was increased following STS exposure, which was blocked by both MAO inhibition and the antioxidant N-acetylcysteine. Therefore our data provide evidence that MAO-A, through its production of reactive oxygen species as a by-product of its catalytic activity on the mitochondrial surface, is recruited by the cell to enhance apoptotic signalling

The expansion of thymopoiesis in neonatal mice is dependent on expression of high mobility group a 2 protein (Hmga2).

Cell number in the mouse thymus increases steadily during the first two weeks after birth. It then plateaus and begins to decline by seven weeks after birth. The factors governing these dramatic changes in cell production are not well understood. The data herein correlate levels of High mobility group A 2 protein (Hmga2) expression with these temporal changes in thymopoiesis. Hmga2 is expressed at high levels in murine fetal and neonatal early T cell progenitors (ETP), which are the most immature intrathymic precursors, and becomes almost undetectable in these progenitors after 5 weeks of age. Hmga2 expression is critical for the initial, exponential expansion of thymopoiesis, as Hmga2 deficient mice have a deficit of ETPs within days after birth, and total thymocyte number is repressed compared to wild type littermates. Finally, our data raise the possibility that similar events occur in humans, because Hmga2 expression is high in human fetal thymic progenitors and falls in these cells during early infancy

Predictors of under Five Years Old Diarrhoeal Disease in Mataniko Informal Settlements in Solomon Islands

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Huddle test measurement of a near Johnson noise limited geophone

In this paper, the sensor noise of two geophone configurations (L-22D and L-4C geophones from Sercel with custom built amplifiers) was measured by performing two huddle tests. It is shown that the accuracy of the results can be significantly improved by performing the huddle test in a seismically quiet environment and by using a large number of reference sensors to remove the seismic foreground signal from the data. Using these two techniques, the measured sensor noise of the two geophone configurations matched the calculated predictions remarkably well in the bandwidth of interest (0.01 Hz–100 Hz). Low noise operational amplifiers OPA188 were utilized to amplify the L-4C geophone to give a sensor that was characterized to be near Johnson noise limited in the bandwidth of interest with a noise value of 10−11 m/Hz⎯⎯⎯⎯⎯√10−11 m/Hz at 1 Hz

Passive-performance, analysis, and upgrades of a 1-ton seismic attenuation system

The 10m Prototype facility at the Albert-Einstein-Institute (AEI) in Hanover, Germany, employs three large seismic attenuation systems to reduce mechanical motion. The AEI Seismic-Attenuation-System (AEI-SAS) uses mechanical anti-springs in order to achieve resonance frequencies below 0.5Hz. This system provides passive isolation from ground motion by a factor of about 400 in the horizontal direction at 4Hz and in the vertical direction at 9Hz. The presented isolation performance is measured under vacuum conditions using a combination of commercial and custom-made inertial sensors. Detailed analysis of this performance led to the design and implementation of tuned dampers to mitigate the effect of the unavoidable higher order modes of the system. These dampers reduce RMS motion substantially in the frequency range between 10 and 100Hz in 6 degrees of freedom. The results presented here demonstrate that the AEI-SAS provides substantial passive isolation at all the fundamental mirror-suspension resonances

Defining the role of oxygen tension in human neural progenitor fate.

Hypoxia augments human embryonic stem cell (hESC) self-renewal via hypoxia-inducible factor 2α-activated OCT4 transcription. Hypoxia also increases the efficiency of reprogramming differentiated cells to a pluripotent-like state. Combined, these findings suggest that low O2 tension would impair the purposeful differentiation of pluripotent stem cells. Here, we show that low O2 tension and hypoxia-inducible factor (HIF) activity instead promote appropriate hESC differentiation. Through gain- and loss-of-function studies, we implicate O2 tension as a modifier of a key cell fate decision, namely whether neural progenitors differentiate toward neurons or glia. Furthermore, our data show that even transient changes in O2 concentration can affect cell fate through HIF by regulating the activity of MYC, a regulator of LIN28/let-7 that is critical for fate decisions in the neural lineage. We also identify key small molecules that can take advantage of this pathway to quickly and efficiently promote the development of mature cell types