831 research outputs found

    Ecosystem Engineering, Anthropogenic Landscapes, and Sea Level Changes Over 8000 Years of Human History in the Eastern Caribbean

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    Upon first arrival of humans to new places anthropogenic disturbances to landscapes commence. Later groups of different people or descendants of the original colonists will make yet additional modifications and so on through time, so that by today the landscape contains a cumulative record of anthropogenic history. We combined the interpretive frameworks of landscape and historical ecology to investigate the anthropogenic trajectories across nine islands of the southern and eastern Caribbean. Microfossils from a series of environmental cores reveal the shifting and cumulative humanization of landscapes from c. 8000 cal yr BP through early European colonial occupations in this region

    Nitric oxide regulates skeletal muscle fatigue, fiber type, microtubule organization, and mitochondrial ATP synthesis efficiency through cGMP-dependent mechanisms

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    Aim: Skeletal muscle nitric oxide–cyclic guanosine monophosphate (NO-cGMP) pathways are impaired in Duchenne and Becker muscular dystrophy partly because of reduced nNOSμ and soluble guanylate cyclase (GC) activity. However, GC function and the consequences of reduced GC activity in skeletal muscle are unknown. In this study, we explore the functions of GC and NO-cGMP signaling in skeletal muscle. Results: GC1, but not GC2, expression was higher in oxidative than glycolytic muscles. GC1 was found in a complex with nNOSμ and targeted to nNOS compartments at the Golgi complex and neuromuscular junction. Baseline GC activity and GC agonist responsiveness was reduced in the absence of nNOS. Structural analyses revealed aberrant microtubule directionality in GC1−/− muscle. Functional analyses of GC1−/− muscles revealed reduced fatigue resistance and postexercise force recovery that were not due to shifts in type IIA–IIX fiber balance. Force deficits in GC1−/− muscles were also not driven by defects in resting mitochondrial adenosine triphosphate (ATP) synthesis. However, increasing muscle cGMP with sildenafil decreased ATP synthesis efficiency and capacity, without impacting mitochondrial content or ultrastructure. Innovation: GC may represent a new target for alleviating muscle fatigue and that NO-cGMP signaling may play important roles in muscle structure, contractility, and bioenergetics. Conclusions: These findings suggest that GC activity is nNOS dependent and that muscle-specific control of GC expression and differential GC targeting may facilitate NO-cGMP signaling diversity. They suggest that nNOS regulates muscle fiber type, microtubule organization, fatigability, and postexercise force recovery partly through GC1 and suggest that NO-cGMP pathways may modulate mitochondrial ATP synthesis efficiency

    Faint NUV/FUV Standards from Swift/UVOT, GALEX and SDSS Photometry

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    At present, the precision of deep ultraviolet photometry is somewhat limited by the dearth of faint ultraviolet standard stars. In an effort to improve this situation, we present a uniform catalog of eleven new faint (u sim17) ultraviolet standard stars. High-precision photometry of these stars has been taken from the Sloan Digital Sky Survey and Galaxy Evolution Explorer and combined with new data from the Swift Ultraviolet Optical Telescope to provide precise photometric measures extending from the Near Infrared to the Far Ultraviolet. These stars were chosen because they are known to be hot (20,000 < T_eff < 50,000 K) DA white dwarfs with published Sloan spectra that should be photometrically stable. This careful selection allows us to compare the combined photometry and Sloan spectroscopy to models of pure hydrogen atmospheres to both constrain the underlying properties of the white dwarfs and test the ability of white dwarf models to predict the photometric measures. We find that the photometry provides good constraint on white dwarf temperatures, which demonstrates the ability of Swift/UVOT to investigate the properties of hot luminous stars. We further find that the models reproduce the photometric measures in all eleven passbands to within their systematic uncertainties. Within the limits of our photometry, we find the standard stars to be photometrically stable. This success indicates that the models can be used to calibrate additional filters to our standard system, permitting easier comparison of photometry from heterogeneous sources. The largest source of uncertainty in the model fitting is the uncertainty in the foreground reddening curve, a problem that is especially acute in the UV.Comment: Accepted for publication in Astrophysical Journal. 31 pages, 13 figures, electronic tables available from ApJ or on reques

    The histone H3K9 demethylase KDM3A promotes anoikis by transcriptionally activating pro-apoptotic genes BNIP3 and BNIP3L

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    Epithelial cells that lose attachment to the extracellular matrix undergo a specialized form of apoptosis called anoikis. Here, using large-scale RNA interference (RNAi) screening, we find that KDM3A, a histone H3 lysine 9 (H3K9) mono- and di-demethylase, plays a pivotal role in anoikis induction. In attached breast epithelial cells, KDM3A expression is maintained at low levels by integrin signaling. Following detachment, integrin signaling is decreased resulting in increased KDM3A expression. RNAi-mediated knockdown of KDM3A substantially reduces apoptosis following detachment and, conversely, ectopic expression of KDM3A induces cell death in attached cells. We find that KDM3A promotes anoikis through transcriptional activation of BNIP3 and BNIP3L, which encode pro-apoptotic proteins. Using mouse models of breast cancer metastasis we show that knockdown of Kdm3a enhances metastatic potential. Finally, we find defective KDM3A expression in human breast cancer cell lines and tumors. Collectively, our results reveal a novel transcriptional regulatory program that mediates anoikis

    Improvements in Speed and Functionality of a 670-GHz Imaging Radar

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    Significant improvements have been made in the instrument originally described in a prior NASA Tech Briefs article: Improved Speed and Functionality of a 580-GHz Imaging Radar (NPO-45156), Vol. 34, No. 7 (July 2010), p. 51. First, the wideband YIG oscillator has been replaced with a JPL-designed and built phase-locked, low-noise chirp source. Second, further refinements to the data acquisition and signal processing software have been performed by moving critical code sections to C code, and compiling those sections to Windows DLLs, which are then invoked from the main LabVIEW executive. This system is an active, single-pixel scanned imager operating at 670 GHz. The actual chirp signals for the RF and LO chains were generated by a pair of MITEQ 2.5 3.3 GHz chirp sources. Agilent benchtop synthesizers operating at fixed frequencies around 13 GHz were then used to up-convert the chirp sources to 15.5 16.3 GHz. The resulting signals were then multiplied 36 times by a combination of off-the-shelf millimeter- wave components, and JPL-built 200- GHz doublers and 300- and 600-GHz triplers. The power required to drive the submillimeter-wave multipliers was provided by JPL-built W-band amplifiers. The receive and transmit signal paths were combined using a thin, high-resistivity silicon wafer as a beam splitter. While the results at present are encouraging, the system still lacks sufficient speed to be usable for practical applications in a contraband detection. Ideally, an image acquisition speed of ten seconds, or a factor of 30 improvement, is desired. However, the system improvements to date have resulted in a factor of five increase in signal acquisition speed, as well as enhanced signal processing algorithms, permitting clearer imaging of contraband objects hidden underneath clothing. In particular, advances in three distinct areas have enabled these performance enhancements: base source phase noise reduction, chirp rate, and signal processing. Additionally, a second pixel was added, automatically reducing the imaging time by a factor of two. Although adding a second pixel to the system doubles the amount of submillimeter components required, some savings in microwave hardware can be realized by using a common low-noise source

    Initial State Interactions for K−K^--Proton Radiative Capture

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    The effects of the initial state interactions on the K−−pK^--p radiative capture branching ratios are examined and found to be quite sizable. A general coupled-channel formalism for both strong and electromagnetic channels using a particle basis is presented, and applied to all the low energy K−−pK^--p data with the exception of the {\it 1s} atomic level shift. Satisfactory fits are obtained using vertex coupling constants for the electromagnetic channels that are close to their expected SU(3) values.Comment: 16 pages, uses revte

    Defining Refractory Migraine: Results of the RHSIS Survey of American Headache Society Members

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    To gauge consensus regarding a proposed definition for refractory migraine proposed by Refractory Headache Special Interest Section, and where its use would be most appropriate. Background.— Headache experts have long recognized that a subgroup of headache sufferers remains refractory to treatment. Although different groups have proposed criteria to define refractory migraine, the definition remains controversial. The Refractory Headache Special Interest Section of the American Headache Society developed a definition through a consensus process, assisted by a literature review and initial membership survey. Design.— A 12-item questionnaire was distributed at the American Headache Society meeting in 2007 during a platform session and at the Refractory Headache Special Interest Section symposium. The same questionnaire was subsequently sent to all American Headache Society members via e-mail. A total of 151 responses from AHS members form the basis of this report. The survey instrument was designed using Survey Monkey. Frequencies and percentages of the survey were used to describe survey responses. Results.— American Headache Society members agreed that a definition for refractory migraine is needed (91%) that it should be added to the International Classification of Headache Disorders-2 (86%), and that refractory forms of non-migraine headache disorders should be defined (87%). Responders believed a refractory migraine definition would be of greatest value in selecting patients for clinical drug trials. The current refractory migraine definition requires a diagnosis of migraine, interference with function or quality of life despite modification of lifestyle factors, and adequate trials of acute and preventive medicines with established efficacy. The proposed criteria for the refractory migraine definition require failing 2 preventive medications to meet the threshold for failure. Although 42% of respondents agreed with the working definition of refractory migraine, 43% favored increasing the number to 3 (50%) or 4 (26%) preventive treatment failures. When respondents were asked if they felt that the proposed definition was appropriate to select patients for invasive procedures (patent foramen ovale repair or stimulators) only 44% agreed. Conclusions.— There is a consensus for a need for a definition for refractory migraine and that it should be added to the International Classification of Headache Disorder-2. There was also general agreement by the responders that refractory forms of non-migraine headache disorders should be defined.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72860/1/j.1526-4610.2009.01370.x.pd

    A Disorder-to-Order Transition Activates an ATP-Independent Membrane Protein Chaperone

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    The 43 kDa subunit of the chloroplast signal recognition particle, cpSRP43, is an ATP-independent chaperone essential for the biogenesis of the light harvesting chlorophyll-binding proteins (LHCP), the most abundant membrane protein family on earth. cpSRP43 is activated by a stromal factor, cpSRP54, to more effectively capture and solubilize LHCPs. The molecular mechanism underlying this chaperone activation is unclear. Here, a combination of hydrogen–deuterium exchange, electron paramagnetic resonance, and NMR spectroscopy experiments reveal that a disorder-to-order transition of the ankyrin repeat motifs in the substrate binding domain of cpSRP43 drives its activation. An analogous coil-to-helix transition in the bridging helix, which connects the ankyrin repeat motifs to the cpSRP54 binding site in the second chromodomain, mediates long-range allosteric communication of cpSRP43 with its activating binding partner. Our results provide a molecular model to explain how the conformational dynamics of cpSRP43 enables regulation of its chaperone activity and suggest a general mechanism by which ATP-independent chaperones with cooperatively folding domains can be regulated
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