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FIGURE 8.

Effects of MPTP on mitochondrial localization of autophagy marker, Parkin. Immunofluorescence microscopy was carried out in differentiated Neuro-2A (Mock and −SRP cells) with and without added MPTP (400 μ m ) for 48 h and the CYP2D6-selective inhibitor quinidine (10 μ m ). Cells were incubated with a 1:1000 dilution (v/v) of primary anti-rabbit antibody to Parkin (Abcam, Cambridge, MA) and co-stained with a 1:500 dilution (v/v) of cytochrome oxidase I (anti-mouse) antibody as a mitochondrion-specific marker (Abcam, Cambridge, MA). The cells were subsequently incubated with Alexa 546-conjugated anti-rabbit and Alexa 488-conjugated anti-mouse IgG for colocalization of fluorescence signals. , mock-transfected cells; , −SRP 2D6-expressing cells. cells with no MPTP treatment; , cells with added MPTP; , cells with added MPTP and quinidine. indicate Pearson coefficients calculated using Volocity 5.3 software.

Drp-1 is a protein involved in mitochondrial dynamics and induces mitochondrial fission as part of quality control during cell division, also during mitochondrial stress ( 43 ). The mitochondrial Drp-1 level in mock-transfected control cells was relatively low ( PARAS ML Sports shoes light grey Footlocker For Sale Top Quality mIuTO4E
A , panel i ), which increases significantly by MPTP treatment ( Prada Loafers for Men On Sale Black Saffiano 2017 7 9 Outlet Pictures jCm6gOChRv
A , panel ii ). Treatment with quinidine did not affect the MPTP-induced Drp-1 levels ( Fig. 9 A , panel iii ). Cells expressing −SRP CYP2D6 also contained relatively low mitochondrial Drp-1 ( Fig. 9 B , panel i ), which was increased by treatment with MPTP ( Fig. 9 B , panel ii , Pearson's coefficient 0.9). Treatment with quinidine, however, significantly reduced the MPTP-induced mitochondrial Drp-1 level ( Fig. 9 B, panel iii ). These results show that MPTP induced mitochondrial localization of Drp-1 as part of mitochondrial stress, which was partly relieved by CYP2D6 inhibitor quinidine. These results together show that mitochondrial CYP2D6 plays a critical role in MPTP-induced mitochondrial dysfunction and autophagy.

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FIGURE 9.

Effects of MPTP on the induction of Drp-1, a marker for mitochondrial fission. Immunofluorescence microscopy was carried out in differentiated Neuro-2A (mock and −SRP cells) with and without MPTP (400 μ m ) for 48 h as described in Diesel V is for Diesel S Spaark Low in Light Gray With Paypal Sale Online Sale Low Cost Visa Payment Cheap Online Cheap Sale Professional S1kBcJQ9
. Cells were incubated with a 1:250 dilution (v/v) of anti-rabbit DRP-1 antibody (Novus Biologicals, Littleton, CO) and co-stained with a 1:500 dilution (v/v) of cytochrome oxidase I (anti-mouse) antibody. The cells were subsequently incubated with Alexa 546-conjugated anti-rabbit and Alexa 488-conjugated anti-mouse IgG for co-localization of fluorescence signals. , mock-transfected; , −SRP CYP2D6-expressing cells. cells with no MPTP treatment; cells with MPTP treatment; cells treated with MPTP and quinidine. indicate Pearson coefficients for co-localization, calculated using Volocity 5.3 software.

Because the mouse is an effective model for studying MPTP-induced Parkinson disease, we determined the effects of MPTP on the primary cortical neurons from mouse brain. These neurons are known to be a mixed population consisting of glutaminergic and GABAergic neurons ( 44 ). We evaluated cell death in control, MPTP-treated, and MPTP + quinidine-treated cells by trypan blue staining method. The trypan blue-positive cells were quantified by manual cell counting from six randomized fields/well. As shown in Fig. 10 , A and B , there was an ∼15% of cell death in control untreated cells, which was increased to 35% in MPTP-treated cells. Quinidine, a CYP2D6 inhibitor, reduced the cell death to ∼25% suggesting that mitochondrial CYP2D6 plays a role in MPTP-induced cell death.

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Extreme Trans-Neptunian Objects May Lead The Way To Planet Nine - Or 10
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In the race towards the discovery of another planet in our solar system, the ninth or tenth depending on how seriously you take the 2 percent of astronomers who demoted Pluto, scientists are striving to calculate its potential orbit using the tracks left by the small bodies that move well beyond Neptune. And the calculations may mean even more than 10 exist.

New calculations confirm that the orbits of the six extreme trans-Neptunian objects that served as a reference to announce the existence of Planet Nine are not as stable as it was thought.

What changed so fast? Earlier this year, astronomers K. Batygin and M. Brown from the California Institute of Technology announced that they had found evidence of the existence of a giant planet with a mass ten times larger than Earth's in the confines of the Solar System. Moving in an unusually elongated orbit, the mysterious planet will take between 10,000 and 20,000 years to complete one revolution around the Sun.

But the media hype left out that it was just based on computer simulations, and they used input data based on the orbits of six extreme trans-Neptunian objects (ETNOs). Specifically, these ETNOs are: Sedna, 2012 VP113, 2004 VN112, 2007 TG422, 2013 RF98 and 2010 GB174.

Assuming that is true, how would the orbits of these six ETNOs evolve if a Planet Nine such as the one proposed by K. Batygin and M. Brown really did exist?

"With the orbit indicated by the Caltech astronomers for Planet Nine, our calculations show that the six ETNOs, which they consider to be the Rosetta Stone in the solution to this mystery, would move in lengthy, unstable orbits," warnbrothers Carlos and Raúl de la Fuente Marcos, two freelance Spanish astronomers, and paid scientist Sverre J. Aarseth from the Institute of Astronomy in Monthly Notices of the Royal Astronomical Society (MNRAS). "These objects would escape from the Solar System in less than 1.5 billion years, -he adds-, and in the case of 2004 VN112, 2007 TG422 and 2013 RF98 they could abandon it in less than 300 million years; what is more important, their orbits would become really unstable in just 10 million years, a really short amount of time in astronomical terms."

May 21, 2018 by Bob Yirka, Phys.org Inexpensive Sperry Cloud Cheap Best FzhCmU5i

A large international team of researchers has found what they are describing as more evidence of the existence of Planet Nine. In their paper posted on the preprint server, the group describes the behavior of a newly discovered distant object as suggestive of an influence of a large planet.

It was just two years ago that astronomers at Caltech proposed the possible existence of a large planet circling the sun—which would make it the ninth known planet in our solar system. The researchers made their prediction based on observations of icy objects that exist at the edge of the solar system—their orbits were clearly being warped by a gravitational mass. They suggested a very distant planet roughly four times the size of Earth, but with 10 times its mass, could account for the odd behavior. If such a planet does exist, it would be quite distant, taking from 10,000 to 20,000 years to make one trip around the sun. Since announcing their initial findings, the team at Caltech has published papers offering more evidence of the planet—the possibility that it could have played a role in tilting the other planets in our solar system, for example. They have also suggested it as an explanation for why objects in the Kuiper Belt orbit in an opposite direction to everything else.

In this new effort, the researchers suggest the behavior of a certain Trans-Neptunian object could very well be due to gravity from Planet Nine. The object, called 2015 BP519 (Caju for short), was first noted approximately three years ago, but it was only recently that the shape of its orbit was found to be very unusual—it lies nearly perpendicular to the plane established by the known planets . What makes the find so compelling is that the team of researchers who first proposed the existence of Planet Nine created a simulation that predicted the orbital angle of just such an object. And it just happened to match with what has been found.

The researchers report that after Caju was first discovered, attempts were made to calculate its Official Site Cheap Price Florsheim Union Plain Toe Oxford Saddle Tan Leather/Suede Mens Lace up casual Shoes Get Authentic For Sale Clearance Exclusive Sale Sneakernews MUHMkDpjC
, but they all failed. Then they added a large planet to the simulations, which resolved the discrepancies. All that is needed now, they suggest, is for someone to actually find the planet.

Explore further: In search of the ninth planet

More information: Discovery and Dynamical Analysis of an Extreme Trans-Neptunian Object with a High Orbital Inclination, arXiv:1805.05355 [astro-ph.EP] arxiv.org/abs/1805.05355

Abstract We report the discovery and dynamical analysis of 2015 BP519, an extreme Trans-Neptunian Object detected detected by the Dark Energy Survey at a heliocentric distance of 55 AU and absolute magnitude Hr= 4.3. The current orbit, determined from a 1110-day observational arc, has semi-major axis a≈ 450 AU, eccentricity e≈ 0.92 and inclination i≈ 54 degrees. With these orbital elements, 2015 BP519 is the most extreme TNO discovered to date, as quantified by the reduced Kozai action, which is is a conserved quantity at fixed semi-major axis a for axisymmetric perturbations. We discuss the orbital stability and evolution of this object in the context of the known Solar System, and find that 2015 BP519 displays rich dynamical behavior, including rapid diffusion in semi-major axis and more constrained variations in eccentricity and inclination. We also consider the long term orbital stability and evolutionary behavior within the context of the Planet Nine Hypothesis, and find that BP519 adds to the circumstantial evidence for the existence of this proposed new member of the Solar System, as it would represent the first member of the population of high-i, ϖ-shepherded TNOs.

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