705 research outputs found
Mtss1 promotes cell-cell junction assembly and stability through the small GTPase Rac1
Cell-cell junctions are an integral part of epithelia and are often disrupted in cancer cells during epithelial-to-mesenchymal transition (EMT), which is a main driver of metastatic spread. We show here that Metastasis suppressor-1 (Mtss1; Missing in Metastasis, MIM), a member of the IMD-family of proteins, inhibits cell-cell junction disassembly in wound healing or HGF-induced scatter assays by enhancing cell-cell junction strength. Mtss1 not only makes cells more resistant to cell-cell junction disassembly, but also accelerates the kinetics of adherens junction assembly. Mtss1 drives enhanced junction formation specifically by elevating Rac-GTP. Lastly, we show that Mtss1 depletion reduces recruitment of F-actin at cell-cell junctions. We thus propose that Mtss1 promotes Rac1 activation and actin recruitment driving junction maintenance. We suggest that the observed loss of Mtss1 in cancers may compromise junction stability and thus promote EMT and metastasis
The N-terminal intrinsically disordered domain of mgm101p is localized to the mitochondrial nucleoid.
The mitochondrial genome maintenance gene, MGM101, is essential for yeasts that depend on mitochondrial DNA replication. Previously, in Saccharomyces cerevisiae, it has been found that the carboxy-terminal two-thirds of Mgm101p has a functional core. Furthermore, there is a high level of amino acid sequence conservation in this region from widely diverse species. By contrast, the amino-terminal region, that is also essential for function, does not have recognizable conservation. Using a bioinformatic approach we find that the functional core from yeast and a corresponding region of Mgm101p from the coral Acropora millepora have an ordered structure, while the N-terminal domains of sequences from yeast and coral are predicted to be disordered. To examine whether ordered and disordered domains of Mgm101p have specific or general functions we made chimeric proteins from yeast and coral by swapping the two regions. We find, by an in vivo assay in S.cerevisiae, that the ordered domain of A.millepora can functionally replace the yeast core region but the disordered domain of the coral protein cannot substitute for its yeast counterpart. Mgm101p is found in the mitochondrial nucleoid along with enzymes and proteins involved in mtDNA replication. By attaching green fluorescent protein to the N-terminal disordered domain of yeast Mgm101p we find that GFP is still directed to the mitochondrial nucleoid where full-length Mgm101p-GFP is targeted
Diffuse Gamma Rays: Galactic and Extragalactic Diffuse Emission
"Diffuse" gamma rays consist of several components: truly diffuse emission
from the interstellar medium, the extragalactic background, whose origin is not
firmly established yet, and the contribution from unresolved and faint Galactic
point sources. One approach to unravel these components is to study the diffuse
emission from the interstellar medium, which traces the interactions of high
energy particles with interstellar gas and radiation fields. Because of its
origin such emission is potentially able to reveal much about the sources and
propagation of cosmic rays. The extragalactic background, if reliably
determined, can be used in cosmological and blazar studies. Studying the
derived "average" spectrum of faint Galactic sources may be able to give a clue
to the nature of the emitting objects.Comment: 32 pages, 28 figures, kapproc.cls. Chapter to the book "Cosmic
Gamma-Ray Sources," to be published by Kluwer ASSL Series, Edited by K. S.
Cheng and G. E. Romero. More details can be found at
http://www.gamma.mpe-garching.mpg.de/~aws/aws.htm
Optimization of total protein and activity assays for the detection of MMP-12 in induced human sputum
<p>Abstract</p> <p>Background</p> <p>Proteolysis of matrix components, in particular elastin, is a major contributing factor to the development of lung diseases such as emphysema and chronic obstructive pulmonary disease (COPD). MMP-12 (macrophage elastase) is a protease known to be involved in the progression of lung disease. The relatively low abundance of MMP-12 has precluded the development of quantitative assays that can accurately measure MMP-12 protein levels and activity across cohorts of healthy and diseased individuals.</p> <p>Methods</p> <p>Commercial antibodies were screened for performance in sandwich ELISA and capture FRET activity assay formats. Precision, accuracy, sensitivity, dilution linearity, and spike recovery were evaluated using sputum samples.</p> <p>Results</p> <p>Total protein and capture FRET activity assays were developed that were sensitive enough to detect MMP-12 in 37 of 38 donor sputum samples. A comparison of results between the two assays shows that a majority of sputum MMP-12 is in the active form. No differences were seen between normal, asthmatic, and COPD donors.</p> <p>Conclusion</p> <p>Sensitive and quantitative assays for both MMP-12 activity and total protein in human induced sputum have been developed. These assays can be used to evaluate MMP-12 as a biomarker for lung disease, and to monitor efficacy of potential therapeutic compounds.</p
Magnetism, FeS colloids, and Origins of Life
A number of features of living systems: reversible interactions and weak
bonds underlying motor-dynamics; gel-sol transitions; cellular connected
fractal organization; asymmetry in interactions and organization; quantum
coherent phenomena; to name some, can have a natural accounting via
interactions, which we therefore seek to incorporate by expanding the horizons
of `chemistry-only' approaches to the origins of life. It is suggested that the
magnetic 'face' of the minerals from the inorganic world, recognized to have
played a pivotal role in initiating Life, may throw light on some of these
issues. A magnetic environment in the form of rocks in the Hadean Ocean could
have enabled the accretion and therefore an ordered confinement of
super-paramagnetic colloids within a structured phase. A moderate H-field can
help magnetic nano-particles to not only overcome thermal fluctuations but also
harness them. Such controlled dynamics brings in the possibility of accessing
quantum effects, which together with frustrations in magnetic ordering and
hysteresis (a natural mechanism for a primitive memory) could throw light on
the birth of biological information which, as Abel argues, requires a
combination of order and complexity. This scenario gains strength from
observations of scale-free framboidal forms of the greigite mineral, with a
magnetic basis of assembly. And greigite's metabolic potential plays a key role
in the mound scenario of Russell and coworkers-an expansion of which is
suggested for including magnetism.Comment: 42 pages, 5 figures, to be published in A.R. Memorial volume, Ed
Krishnaswami Alladi, Springer 201
Spider Silk Constructs Enhance Axonal Regeneration and Remyelination in Long Nerve Defects in Sheep
BACKGROUND: Surgical reapposition of peripheral nerve results in some axonal regeneration and functional recovery, but the clinical outcome in long distance nerve defects is disappointing and research continues to utilize further interventional approaches to optimize functional recovery. We describe the use of nerve constructs consisting of decellularized vein grafts filled with spider silk fibers as a guiding material to bridge a 6.0 cm tibial nerve defect in adult sheep. METHODOLOGY/PRINCIPAL FINDINGS: The nerve constructs were compared to autologous nerve grafts. Regeneration was evaluated for clinical, electrophysiological and histological outcome. Electrophysiological recordings were obtained at 6 months and 10 months post surgery in each group. Ten months later, the nerves were removed and prepared for immunostaining, electrophysiological and electron microscopy. Immunostaining for sodium channel (NaV 1.6) was used to define nodes of Ranvier on regenerated axons in combination with anti-S100 and neurofilament. Anti-S100 was used to identify Schwann cells. Axons regenerated through the constructs and were myelinated indicating migration of Schwann cells into the constructs. Nodes of Ranvier between myelin segments were observed and identified by intense sodium channel (NaV 1.6) staining on the regenerated axons. There was no significant difference in electrophysiological results between control autologous experimental and construct implantation indicating that our construct are an effective alternative to autologous nerve transplantation. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that spider silk enhances Schwann cell migration, axonal regrowth and remyelination including electrophysiological recovery in a long-distance peripheral nerve gap model resulting in functional recovery. This improvement in nerve regeneration could have significant clinical implications for reconstructive nerve surgery
Evolutionary and pulsational properties of white dwarf stars
Abridged. White dwarf stars are the final evolutionary stage of the vast
majority of stars, including our Sun. The study of white dwarfs has potential
applications to different fields of astrophysics. In particular, they can be
used as independent reliable cosmic clocks, and can also provide valuable
information about the fundamental parameters of a wide variety of stellar
populations, like our Galaxy and open and globular clusters. In addition, the
high densities and temperatures characterizing white dwarfs allow to use these
stars as cosmic laboratories for studying physical processes under extreme
conditions that cannot be achieved in terrestrial laboratories. They can be
used to constrain fundamental properties of elementary particles such as axions
and neutrinos, and to study problems related to the variation of fundamental
constants.
In this work, we review the essentials of the physics of white dwarf stars.
Special emphasis is placed on the physical processes that lead to the formation
of white dwarfs as well as on the different energy sources and processes
responsible for chemical abundance changes that occur along their evolution.
Moreover, in the course of their lives, white dwarfs cross different
pulsational instability strips. The existence of these instability strips
provides astronomers with an unique opportunity to peer into their internal
structure that would otherwise remain hidden from observers. We will show that
this allows to measure with unprecedented precision the stellar masses and to
infer their envelope thicknesses, to probe the core chemical stratification,
and to detect rotation rates and magnetic fields. Consequently, in this work,
we also review the pulsational properties of white dwarfs and the most recent
applications of white dwarf asteroseismology.Comment: 85 pages, 28 figures. To be published in The Astronomy and
Astrophysics Revie
Matrix metalloproteinases in lung biology
Despite much information on their catalytic properties and gene regulation, we actually know very little of what matrix metalloproteinases (MMPs) do in tissues. The catalytic activity of these enzymes has been implicated to function in normal lung biology by participating in branching morphogenesis, homeostasis, and repair, among other events. Overexpression of MMPs, however, has also been blamed for much of the tissue destruction associated with lung inflammation and disease. Beyond their role in the turnover and degradation of extracellular matrix proteins, MMPs also process, activate, and deactivate a variety of soluble factors, and seldom is it readily apparent by presence alone if a specific proteinase in an inflammatory setting is contributing to a reparative or disease process. An important goal of MMP research will be to identify the actual substrates upon which specific enzymes act. This information, in turn, will lead to a clearer understanding of how these extracellular proteinases function in lung development, repair, and disease
A change in the optical polarization associated with a gamma-ray flare in the blazar 3C 279
It is widely accepted that strong and variable radiation detected over all
accessible energy bands in a number of active galaxies arises from a
relativistic, Doppler-boosted jet pointing close to our line of sight. The size
of the emitting zone and the location of this region relative to the central
supermassive black hole are, however, poorly known, with estimates ranging from
light-hours to a light-year or more. Here we report the coincidence of a
gamma-ray flare with a dramatic change of optical polarization angle. This
provides evidence for co-spatiality of optical and gamma-ray emission regions
and indicates a highly ordered jet magnetic field. The results also require a
non-axisymmetric structure of the emission zone, implying a curved trajectory
for the emitting material within the jet, with the dissipation region located
at a considerable distance from the black hole, at about 10^5 gravitational
radii.Comment: Published in Nature issued on 18 February 2010. Corresponding
authors: Masaaki Hayashida and Greg Madejsk
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