The effects of mechanical strain on adhesion in Myh9-ablated podocytes

Myh9 is a gene that encodes for non-muscle myosin IIA (NM-IIA), an actin cytoskeleton component and protein involved in cell movement and adhesion in most cells, including podocytes. Autosomal dominant mutations in NM-IIA have been associated with focal segmental glomerular sclerosis (FSGS) in patients with the mutation. Furthermore, a strong association has been discovered between genetic variation in the Myh9 region on chromosome 22, and the increased risk of chronic kidney disease in African Americans. Later studies by Johnstone et al. using podocyte specific, Myh9 KO in mice showed that knocking out this gene alone was not enough to cause proteinuria or glomerular sclerosis. However, in our own laboratory we have found that when these same mice are exposed to models of glomerular hypertension, glomerular damage is promoted. This damage was preceded by evidence of podocyte loss in urine and tissue. Podocyte loss is a hallmark of kidney disease, and while it is known to occur in vivo, the mechanisms behind this phenomenon are unknown. It is believed that increase in glomerular capillary blood pressure is likely to be a strong contributing factor. Based on these findings, we hypothesized that the mechanical strain in the form of stretch, occurring during hypertension, may act as a second hit to Myh9 ablation in podocytes, causing changes in podocytes ability to adhere to the glomerular basement membrane (GBM), ultimately leading to the pathology seen in patients. To test this, we knocked down Myh9 in immortalized mouse podocytes cultured on flexible silicon membranes and exposed them to mechanical stretch for 24hrs. Cell adhesion was evaluated via cell attachment assays. Cell morphology and focal adhesions (FA) were examined using immunofluorescence and quantified using imageJ. Our results showed a significant decrease in transduced cells attached to the membrane after stretch, as well as an increase in FA size and number in cells that underwent stretch, except in the Myh9 knockdown. Cells with Myh9 knockdown also showed marked increase in area, with a decrease in FA size and number after exposure to stretch. These results support our hypothesis that Myh9 mutations may be a contributing factor to podocyte loss in patients with hypertension and chronic kidney disease

A method for governing spacecraft evasive maneuvering

May 1986Also issued as an M.S. thesis, Massachusetts Institute of Technology. Dept. of Aeronautics and Astronautics, 1986Includes bibliographical references (p. 249-251)A computer program is developed to govern the evasive maneuvering of a spacecraft in response to an anti-spacecraft missile threat in regions of space where drag is not significant. With a view to circumventing the need to numerically integrate the equations of motion for both vehicles to predict future position and velocity along their trajectories, the methods of astrodynamics are used to determine the unissile's orbit from two vector position fixes over time so it can be compared -to the spacecraft's orbit, determined from a position and velocity vector. The transfer time required for the missile to reach the spacecraft's altitude is determined and the future position of the missile is predicted so that a future relative position vector between the spacecraft and missile can be found. If it is found that the missile will intercept the spacecraft at the future time, appropriate evasive action is initiated for the spacecraft. A maneuver to any point in three-dimensional space can be targeted by specifying the magnitude and direction of the miss-distance desired, and velocityto- be-gained calculations are done as an aid to making maneuvering decisions. To test the assumptions of the astrodynamic techniques in the program, a fourth-order Runga-Kutta numerical integration technique was implemented in the program and is used to update all current trajectory data points. Spacecraft engine thrust, if an impulsive maneuver is not selected, atmospheric drag, and higher order gravitational harmonics are modelled and included in the integration of the equations of motion for both vehicles. When the trajectories of the vehicles were fully integrated to the predicted intercept time, the integrated data points could then be compared to those generated through the astrodynamic techniques. It was found that agreement between integrated and astrodynamic data points could typically be obtained to the third or fourth decimal place in kilometers in scenarios where drag was not significant. The astrodynamic techniques were found to be able to predict intercept and provide information for maneuvering the spacecraft in real-time for simulations run on a VAX 11/750, while the integration techniques experienced a time lag in updating trajectories which was dependent on the integration step size used

Preparation and catalytic evaluation of ruthenium–nickel dendrimer encapsulated nanoparticles via intradendrimer redox displacement of nickel nanoparticles

Ru and Ru_xNi_(30) dendrimer encapsulated nanoparticles (DENs) were synthesized using a redox-displacement method. DEN catalytic activity for the reduction of p-nitrophenol was evaluated and found to be dependent on the ratio of metals present

Lithium atom interferometer using laser diffraction : description and experiments

We have built and operated an atom interferometer of the Mach-Zehnder type. The atomic wave is a supersonic beam of lithium seeded in argon and the mirrors and beam-splitters for the atomic wave are based on elastic Bragg diffraction on laser standing waves at 671 nm. We give here a detailed description of our experimental setup and of the procedures used to align its components. We then present experimental signals, exhibiting atomic interference effects with a very high visibility, up to 84.5 %. We describe a series of experiments testing the sensitivity of the fringe visibility to the main alignment defects and to the magnetic field gradient.Comment: 8 avril 200

Metabolic analysis of the soil microbe Dechloromonas aromatica str. RCB: indications of a surprisingly complex life-style and cryptic anaerobic pathways for aromatic degradation

<p>Abstract</p> <p>Background</p> <p>Initial interest in <it>Dechloromonas aromatica </it>strain RCB arose from its ability to anaerobically degrade benzene. It is also able to reduce perchlorate and oxidize chlorobenzoate, toluene, and xylene, creating interest in using this organism for bioremediation. Little physiological data has been published for this microbe. It is considered to be a free-living organism.</p> <p>Results</p> <p>The <it>a priori </it>prediction that the <it>D. aromatica </it>genome would contain previously characterized "central" enzymes to support anaerobic aromatic degradation of benzene proved to be false, suggesting the presence of novel anaerobic aromatic degradation pathways in this species. These missing pathways include the benzylsuccinate synthase (<it>bss</it>ABC) genes (responsible for fumarate addition to toluene) and the central benzoyl-CoA pathway for monoaromatics. In depth analyses using existing TIGRfam, COG, and InterPro models, and the creation of <it>de novo </it>HMM models, indicate a highly complex lifestyle with a large number of environmental sensors and signaling pathways, including a relatively large number of GGDEF domain signal receptors and multiple quorum sensors. A number of proteins indicate interactions with an as yet unknown host, as indicated by the presence of predicted cell host remodeling enzymes, effector enzymes, hemolysin-like proteins, adhesins, NO reductase, and both type III and type VI secretory complexes. Evidence of biofilm formation including a proposed exopolysaccharide complex and exosortase (epsH) are also present. Annotation described in this paper also reveals evidence for several metabolic pathways that have yet to be observed experimentally, including a sulphur oxidation (<it>sox</it>FCDYZAXB) gene cluster, Calvin cycle enzymes, and proteins involved in nitrogen fixation in other species (including RubisCo, ribulose-phosphate 3-epimerase, and nif gene families, respectively).</p> <p>Conclusion</p> <p>Analysis of the <it>D. aromatica </it>genome indicates there is much to be learned regarding the metabolic capabilities, and life-style, for this microbial species. Examples of recent gene duplication events in signaling as well as dioxygenase clusters are present, indicating selective gene family expansion as a relatively recent event in <it>D. aromatica</it>'s evolutionary history. Gene families that constitute metabolic cycles presumed to create <it>D. aromatica'</it>s environmental 'foot-print' indicate a high level of diversification between its predicted capabilities and those of its close relatives, <it>A. aromaticum </it>str EbN1 and <it>Azoarcus </it>BH72.</p

[Fe II] and H2 filaments in the Supernova Remnant G11.2-0.3: Supernova Ejecta and Presupernova Circumstellar Wind

We present the results of near-infrared imaging and spectroscopic observations of the young, core-collapse supernova remnant (SNR) G11.2-0.3. In the [Fe II] 1.644 um image, we first discover long, clumpy [Fe II] filaments within the radio shell of the SNR, together with some faint, knotty features in the interior of the remnant. We have detected several [Fe II] lines and HI Br-G line toward the peak position of the bright southeastern [Fe II] filament. The derived extinction is large (Av=13 mag) and it is the brightest [Fe II] filament detected toward SNRs to date. By analyzing two [Fe II] 1.644 um images obtained in 2.2 yrs apart, we detect a proper motion corresponding to an expansion rate of 0.''035 (0.''013) /yr [or 830 (310) km/s]. We also discover two small H2 filaments. One is bright and along the SE boundary of the radio shell, while the other is faint and just outside of its NE boundary. We have detected H2 (2-1) S(3) line toward the former filament and derive an excitation temperature of 2,100 K. We suggest that the H2 filaments are dense clumps in a presupernova circumstellar wind swept up by the SNR shock while the [Fe II] filaments are probably composed of both shocked wind material and shocked supernova (SN) ejecta. The distribution of [Fe II] filaments may indicate that the SN explosion in G11.2-0.3 was asymmetric as in Cassiopeia A. Our results support the suggestion that G11.2-0.3 is a remnant of a SN IIL/b interacting with a dense red supergiant wind.Comment: 30 pages with 10 figures, To appear in the Astrophysical Journa