331 research outputs found
Cell Signaling by Receptor Tyrosine Kinases
Recent structural studies of receptor tyrosine kinases (RTKs) have revealed unexpected diversity in the mechanisms of their activation by growth factor ligands. Strategies for inducing dimerization by ligand binding are surprisingly diverse, as are mechanisms that couple this event to activation of the intracellular tyrosine kinase domains. As our understanding of these details becomes increasingly sophisticated, it provides an important context for therapeutically countering the effects of pathogenic RTK mutations in cancer and other diseases. Much remains to be learned, however, about the complex signaling networks downstream from RTKs and how alterations in these networks are translated into cellular responses
Thermodynamic Properties of trans-1,3,3,3-tetrafluoropropene [R1234ze(E)]: Measurements of Density and Vapor Pressure and a Comprehensive Equation of State
Ala-insertion scanning mutagenesis of the glycophorin A transmembrane helix
Alanine insertions into the glycophorinA transmembrane helix are found to disrupthelix-helix dimerization in a way thatis fully consistentwith earlier saturation mutagenesis datas,uggesting that Ala-insertion scanning can be used to rapidly map the approximate locatiofn structurally and/or functionally importantsegments in trans-membrane helice
Live cell imaging with protein domains capable of recognizing phosphatidylinositol 4,5-bisphosphate; a comparative study
<p>Abstract</p> <p>Background</p> <p>Phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)<it>P</it><sub>2</sub>] is a critically important regulatory phospholipid found in the plasma membrane of all eukaryotic cells. In addition to being a precursor of important second messengers, PtdIns(4,5)<it>P</it><sub>2 </sub>also regulates ion channels and transporters and serves the endocytic machinery by recruiting clathrin adaptor proteins. Visualization of the localization and dynamic changes in PtdIns(4,5)<it>P</it><sub>2 </sub>levels in living cells is critical to understanding the biology of PtdIns(4,5)<it>P</it><sub>2</sub>. This has been mostly achieved with the use of the pleckstrin homology (PH) domain of PLCδ1 fused to GFP. Here we report on a comparative analysis of several recently-described yeast PH domains as well as the mammalian Tubby domain to evaluate their usefulness as PtdIns(4,5)<it>P</it><sub>2 </sub>imaging tools.</p> <p>Results</p> <p>All of the yeast PH domains that have been previously shown to bind PtdIns(4,5)<it>P</it><sub>2 </sub>showed plasma membrane localization but only a subset responded to manipulations of plasma membrane PtdIns(4,5)<it>P</it><sub>2</sub>. None of these domains showed any advantage over the PLCδ1PH-GFP reporter and were compromised either in their expression levels, nuclear localization or by causing peculiar membrane structures. In contrast, the Tubby domain showed high membrane localization consistent with PtdIns(4,5)<it>P</it><sub>2 </sub>binding and displayed no affinity for the soluble headgroup, Ins(1,4,5)P<sub>3</sub>. Detailed comparison of the Tubby and PLCδ1PH domains showed that the Tubby domain has a higher affinity for membrane PtdIns(4,5)<it>P</it><sub>2 </sub>and therefore displays a lower sensitivity to report on changes of this lipid during phospholipase C activation.</p> <p>Conclusion</p> <p>These results showed that both the PLCδ1PH-GFP and the GFP-Tubby domain are useful reporters of PtdIns(4,5)<it>P</it><sub>2 </sub>changes in the plasma membrane, with distinct advantages and disadvantages. While the PLCδ1PH-GFP is a more sensitive reporter, its Ins(1,4,5)P<sub>3 </sub>binding may compromise its accuracy to measure PtdIns(4,5)<it>P</it><sub>2</sub>changes. The Tubby domain is more accurate to report on PtdIns(4,5)<it>P</it><sub>2 </sub>but its higher affinity and lower sensitivity may limit its utility when phospholipase C activation is only moderate. These studies also demonstrated that similar changes in PtdIns(4,5)<it>P</it><sub>2 </sub>levels in the plasma membrane can differentially regulate multiple effectors if they display different affinities to PtdIns(4,5)<it>P</it><sub>2</sub>.</p
Titan Science with the James Webb Space Telescope (JWST)
The James Webb Space Telescope (JWST), scheduled for launch in 2018, is the
successor to the Hubble Space Telescope (HST) but with a significantly larger
aperture (6.5 m) and advanced instrumentation focusing on infrared science
(0.6-28.0 m ). In this paper we examine the potential for scientific
investigation of Titan using JWST, primarily with three of the four
instruments: NIRSpec, NIRCam and MIRI, noting that science with NIRISS will be
complementary. Five core scientific themes are identified: (i) surface (ii)
tropospheric clouds (iii) tropospheric gases (iv) stratospheric composition and
(v) stratospheric hazes. We discuss each theme in depth, including the
scientific purpose, capabilities and limitations of the instrument suite, and
suggested observing schemes. We pay particular attention to saturation, which
is a problem for all three instruments, but may be alleviated for NIRCam
through use of selecting small sub-arrays of the detectors - sufficient to
encompass Titan, but with significantly faster read-out times. We find that
JWST has very significant potential for advancing Titan science, with a
spectral resolution exceeding the Cassini instrument suite at near-infrared
wavelengths, and a spatial resolution exceeding HST at the same wavelengths. In
particular, JWST will be valuable for time-domain monitoring of Titan, given a
five to ten year expected lifetime for the observatory, for example monitoring
the seasonal appearance of clouds. JWST observations in the post-Cassini period
will complement those of other large facilities such as HST, ALMA, SOFIA and
next-generation ground-based telescopes (TMT, GMT, EELT).Comment: 50 pages, including 22 figures and 2 table
Seasonal evolution of Titan's dark polar hood: midsummer disappearance observed by the Hubble Space Telescope
Concentrated Perchlorate at the Mars Phoenix Landing Site: Evidence for Thin Film Liquid Water on Mars
NASA\u27s Phoenix mission, which landed on the northern plains of Mars in 2008, returned evidence of the perchlorate anion distributed evenly throughout the soil column at the landing site. Here, we use spectral data from Phoenix\u27s Surface Stereo Imager to map the distribution of perchlorate salts at the Phoenix landing site, and find that perchlorate salt has been locally concentrated into subsurface patches, similar to salt patches that result from aqueous dissolution and redistribution on Earth. We propose that thin films of liquid water are responsible for translocating perchlorate from the surface to the subsurface, and for concentrating it in patches. The thin films are interpreted to result from melting of minor ice covers related to seasonal and long-term obliquity cycles
Dust aerosol, clouds, and the atmospheric optical depth record over 5 Mars years of the Mars Exploration Rover mission
Dust aerosol plays a fundamental role in the behavior and evolution of the
Martian atmosphere. The first five Mars years of Mars Exploration Rover data
provide an unprecedented record of the dust load at two sites. This record is
useful for characterization of the atmosphere at the sites and as ground truth
for orbital observations. Atmospheric extinction optical depths have been
derived from solar images after calibration and correction for time-varying
dust that has accumulated on the camera windows. The record includes local,
regional, and globally extensive dust storms. Comparison with contemporaneous
thermal infrared data suggests significant variation in the size of the dust
aerosols, with a 1 {\mu}m effective radius during northern summer and a 2
{\mu}m effective radius at the onset of a dust lifting event. The solar
longitude (LS) 20-136{\deg} period is also characterized by the presence of
cirriform clouds at the Opportunity site, especially near LS=50 and 115{\deg}.
In addition to water ice clouds, a water ice haze may also be present, and
carbon dioxide clouds may be present early in the season. Variations in dust
opacity are important to the energy balance of each site, and work with
seasonal variations in insolation to control dust devil frequency at the Spirit
site.Comment: 60 pages, 12 figures, to be published in Icaru
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