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

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

Decoupling of the ϵ\epsilon-scalar mass in softly broken supersymmetry

It has been shown recently that the introduction of an unphysical $\epsilon$-scalar mass $\tilde{m}$ is necessary for the proper renormalization of softly broken supersymmetric theories by dimensional reduction (\drbar). In these theories, both the two-loop $\beta$-functions of the scalar masses and their one-loop finite corrections depend on $\tilde{m}^2$. We find, however, that the dependence on $\tilde{m}^2$ can be completely removed by slightly modifying the \drbar renormalization scheme. We also show that previous \drbar calculations of one-loop corrections in supersymmetry which ignored the $\tilde{m}^2$ contribution correspond to using this modified scheme.Comment: 7 pages, LTH-336, NUB-3094-94TH, KEK-TH-40

The silicon trypanosome

African trypanosomes have emerged as promising unicellular model organisms for the next generation of systems biology. They offer unique advantages, due to their relative simplicity, the availability of all standard genomics techniques and a long history of quantitative research. Reproducible cultivation methods exist for morphologically and physiologically distinct life-cycle stages. The genome has been sequenced, and microarrays, RNA-interference and high-accuracy metabolomics are available. Furthermore, the availability of extensive kinetic data on all glycolytic enzymes has led to the early development of a complete, experiment-based dynamic model of an important biochemical pathway. Here we describe the achievements of trypanosome systems biology so far and outline the necessary steps towards the ambitious aim of creating a , a comprehensive, experiment-based, multi-scale mathematical model of trypanosome physiology. We expect that, in the long run, the quantitative modelling enabled by the Silicon Trypanosome will play a key role in selecting the most suitable targets for developing new anti-parasite drugs

The ACS Survey of Galactic Globular Clusters: M54 and Young Populations in the Sagittarius Dwarf Spheroidal Galaxy

We present new Hubble Space Telescope photometry of the massive globular cluster M54 (NGC 6715) and the superposed core of the tidally disrupted Sagittarius (Sgr) dSph galaxy as part of the ACS Survey of Galactic Globular Clusters. Our deep (F606W~26.5), high-precision photometry yields an unprecedentedly detailed color-magnitude diagram showing the extended blue horizontal branch and multiple main sequences of the M54+Sgr system. The distance and reddening to M54 are revised usingboth isochrone and main-sequence fitting to (m-M)_0=17.27 and E(B-V)=0.15. Preliminary assessment finds the M54+Sgr field to be dominated by the old metal-poor populations of Sgr and the globular cluster. Multiple turnoffs indicate the presence of at least two intermediate-aged star formation epochs with 4 and 6 Gyr ages and [Fe/H]=-0.4 to -0.6. We also clearly show, for the first time, a prominent, 2.3 Gyr old Sgr population of near-solar abundance. A trace population of even younger (0.1-0.8 Gyr old), more metal-rich ([Fe/H]\sim0.6) stars is also indicated. The Sgr age-metallicity relation is consistent with a closed-box model and multiple (4-5) star formation bursts over the entire life of the satellite, including the time since Sgr began disrupting.Comment: Accepted to ApJ Letter; 11 pages, 2 figures; figure 1 uploaded as jpg; paper in ApJ format with full-resolution figures available at: http://www.astro.ufl.edu/~ata/public_hstgc/paperIV/paperIV.p

A Survey of Methods for Data Inclusion in System Dynamics Models

In 1980, Jay Forrester enumerated three types of data needed to develop the structure and decision rules in models: numerical, written and mental data, in increasing order of importance. While this prioritization is appropriate, it is numerical data that has experienced the most development in the 25 years since Forester made his enumeration. In this paper, we’ll focus on how numerical data can be incorporated into models when written and mental data are known, and survey the techniques for doing so

The ACS Survey Of Globular Clusters. V. Generating A Comprehensive Star Catalog For Each Cluster

The ACS Survey of Globular Clusters has used Hubble Space Telescope's Wide-Field Channel to obtain uniform imaging of 65 of the nearest globular clusters to provide an extensive homogeneous data set for a broad range of scientific investigations. The survey goals required not only a uniform observing strategy, but also a uniform reduction strategy. To this end, we designed a sophisticated software program to process the cluster data in an automated way. The program identifies stars simultaneously in the multiple dithered exposures for each cluster and measures them using the best available point-spread function models. We describe here in detail the program's rationale, algorithms, and output. The routine was also designed to perform artificial-star tests, and we ran a standard set of similar to 10(5) tests for each cluster in the survey. The catalog described here will be exploited in a number of upcoming papers and will eventually be made available to the public via the World Wide Web.Astronom

Measuring Dust Attenuation Curves of SINGS/KINGFISH Galaxies Using Swift/UVOT Photometry

We present Swift/Ultraviolet Optical Telescope (UVOT) integrated light photometry of the Spitzer Infrared Nearby Galaxies Survey (SINGS) and the Key Insights on Nearby Galaxies: A Far-Infrared Survey with Herschel (KINGFISH) samples of nearby galaxies. Combining the Swift/UVOT data with archival photometry, we investigate a variety of dust attenuation curves derived using MCSED, a flexible spectral energy distribution fitting code. We fit the panchromatic data using three different star formation history (SFH) parameterizations: a decaying exponential, a double power law, and a piecewise function with breaks at physically motivated ages. We find that the average attenuation law of the sample changes slightly based on the SFH assumed. Specifically, the exponential SFH leads to the shallowest attenuation curves. Using simulated data, we also find the exponential SFH fails to outperform the more complex SFHs. Finally, we find a systematic offset in the derived bump strength between SED fits with and without UVOT data, where the inclusion of UVOT data leads to smaller bump strengths, highlighting the importance of the UVOT data. This discrepancy is not seen in fits to mock photometry. Understanding dust attenuation in the local universe is key to understanding high redshift objects where rest-frame far-infrared data is unavailable.Comment: 30 pages, 13 figures, accepted for publication in Ap

Regularization Dependence of Running Couplings in Softly Broken Supersymmetry

We discuss the dependence of running couplings on the choice of regularization method in a general softly-broken N=1 supersymmetric theory. Regularization by dimensional reduction respects supersymmetry, but standard dimensional regularization does not. We find expressions for the differences between running couplings in the modified minimal subtraction schemes of these two regularization methods, to one loop order. We also find the two-loop renormalization group equations for gaugino masses in both schemes, and discuss the application of these results to the Minimal Supersymmetric Standard Model.Comment: 11 pages. v2: Signs of equations (1.2) and (4.2) are fixe