The ChIP-seq-defined networks of Bcl-3 gene binding support its required role in skeletal muscle atrophy

NF-kappaB transcriptional activation is required for skeletal muscle disuse atrophy. We are continuing to study how the activation of NF-kB regulates the genes that encode the protein products that cause atrophy. Using ChIP-sequencing we found that Bcl-3, an NF-kB transcriptional activator required for atrophy, binds to the promoters of a number of genes whose collective function describes two major aspects of muscle wasting. By means of bioinformatics analysis of ChIP-sequencing data we found Bcl-3 to be directing transcription networks of proteolysis and energy metabolism. The proteolytic arm of the Bcl-3 networks includes many E3 ligases associated with proteasomal protein degradation, including that of the N-end rule pathway. The metabolic arm appears to be involved in organizing the change from oxidative phosphorylation to glycolysis in atrophying muscle. For one gene, MuRF1, ChIP-sequencing data identified the location of Bcl-3 and p50 binding in the promoter region which directed the creation of deletant and base-substitution mutations of MuRF1 promoter constructs to determine the effect on gene transcription. The results provide the first direct confirmation that the NF-kB binding site is involved in the muscle unloading regulation of MuRF1. Finally, we have combined the ChIP-sequencing results with gene expression microarray data from unloaded muscle to map several direct targets of Bcl-3 that are transcription factors whose own targets describe a set of indirect targets for NF-kB in atrophy. ChIP-sequencing provides the first molecular explanation for the finding that Bcl3 knockout mice are resistant to disuse muscle atrophy. Mapping the transcriptional regulation of muscle atrophy requires an unbiased analysis of the whole genome, which we show is now possible with ChIP-sequencing.R01 AR041705 - NIAMS NIH HHS; R01 AR060217 - NIAMS NIH HHS; AR041705 - NIAMS NIH HHS; AR060217 - NIAMS NIH HH

A key role for leukemia inhibitory factor in C26 cancer cachexia

Cachexia is an exacerbating event in many types of cancer that is strongly associated with a poor prognosis. We have identified cytokine, signaling, and transcription factors that are required for cachexia in the mouse C26 colon carcinoma model of cancer. C2C12 myotubes treated with conditioned medium from C26 cancer cells induced atrophy and activated a STAT-dependent reporter gene but not reporter genes dependent on SMAD, FOXO, C/EBP, NF-κB, or AP-1. Of the gp130 family members IL-11, IL-6, oncostatin M (OSM), and leukemia inhibitory factor (LIF), only OSM and LIF were sufficient to activate the STAT reporter in myotubes. LIF was elevated in C26 conditioned medium (CM), but IL-6, OSM, TNFα, and myostatin were not. A LIF-blocking antibody abolished C26 CM-induced STAT reporter activation, STAT3 phosphorylation, and myotube atrophy but blocking antibodies to IL-6 or OSM did not. JAK2 inhibitors also blocked C26 CM-induced STAT reporter activation, STAT3 phosphorylation, and atrophy in myotubes. LIF at levels found in the C26 CM was sufficient for STAT reporter activation and atrophy in myotubes. In vivo, an increase in serum LIF preceded the increase in IL-6 in mice with C26 tumors. Overexpression of a dominant negative Stat3Cβ-EGFP gene in myotubes and in mouse muscle blocked the atrophy caused by C26 CM or C26 tumors, respectively. Taken together, these data support an important role of LIF-JAK2-STAT3 in C26 cachexia and point to a therapeutic approach for at least some types of cancer cachexia.R01 AR060217 - NIAMS NIH HHS; UL1 TR000157 - NCATS NIH HHS; UL1-TR000157 - NCATS NIH HHShttp://www.jbc.org/content/290/32/19976.full.pdf?sid=936d126d-814b-4f54-961d-0e98caa31314Published versio

Determination for the modal age level for the grades IV and VI of the difficulty of the principle: a body at rest remains at rest, and a body in motion continues to move at constant speed along a straight line, unless the body is acted upon in either case by an unbalanced force.

Thesis (Ed.M.)--Boston Universit

Two-Dimensional Intercomparison of Stratospheric Models

A detailed record is provided for the examination of fundamental differences in photochemistry and transport among atmospheric models. The results of 16 different modeling groups are presented for several model experiments

What screening tests should you use to evaluate a man with low testosterone?

Obtain a repeat morning testosterone level, as well as levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin to help understand the cause of low testosterone when there is a lack of adequate empiric evidence to guide evaluation, advise the experts. When low or normal FSH and LH levels accompany low testosterone, evaluation of the pituitary gland is recommended. Chromosomal studies are indicated in prepubertal males with low testosterone and elevated FSH and LH levels to assess for Klinefelter syndrome. Perform a semen analysis if fertility is an issue. Bone densitometry is indicated in men with chronic hypogonadism to identify increased risk of hip fracture (strength of all recommendations: C, consensus guidelines and disease-oriented evidence)

Predicted rocket and shuttle effects on stratospheric ozone

The major chemical effluents of either solid- or liquid-fueled rockets that can potentially perturb stratospheric ozone include chlorine compounds (HCl), nitrogen compounds (NO(x)), and hydrogen compounds (H2 and H2O). Radicals (Cl, ClO, H, OH, HO2, NO, and NO2) formed directly or indirectly from rocket exhaust can cause the catalytic destruction of ozone. Other exhaust compounds that could presumably lead to ozone destruction either by direct reaction with ozone or by providing a surface for heterogeneous processes include the particulates Al2O3, ice, and soot. These topics are discussed in terms of the possible effects of rocket exhausts on stratospheric ozone

Sizing studies on pilot-oven coke, comparison with commercial coke-size,

Bibliography: p. 3

Multi-Spectral Visual Crop Assessment Under Limited Data Constraints

In an era of climate change and global population growth, deep learning based multi-spectral imaging has the potential to significantly assist in production management across a wide range of agricultural and food production domains. A key challenge however in applying state-of-the-art methods is that they, unlike classical hand crafted methods, are usually thought of as being only useful when significant amounts of data are available. In this paper we investigate this hypothesis by examining the performance of state-of-the-art deep learning methods when applied to a restricted data set that is not easily bootstrapped through pre-trained image processing networks. We demonstrate that significant result improvement can be obtained from deep residual networks over a baseline image processing model -- even in the case where data collection is highly expensive and pre-trained networks cannot be easily built upon. Our work also constitutes a useful contribution to understanding the benefit of applying deep image multi-spectral processing techniques to the agri-food domain

Non-Coherent Ground-Based Moving Target Indicator

Control Systems Laboratory changed its name to Coordinated Science LaboratoryContract DA-11-022-ORD-72

Combined Spectroscopic and Photometric Analysis of Flares in the Dwarf M Star EV Lacertae

We report results of an observing campaign to study the dwarf M flare star EV Lacertae. Between October 2021 and January 2022 we obtained concurrent B band photometry and low resolution spectroscopy of EV Lac on 39 occasions during 10 of which we observed flares with amplitude greater than 0.1 magnitude. Spectra were calibrated in absolute flux using concurrent photometry and flare-only spectra obtained by subtracting mean quiescent spectra. We measured B band flare energies between Log E = 30.8 and 32.6 erg. In the brightest flares we measured temporal development of flare flux in H I and He I emission lines and in the adjacent continuum and found that flux in the continuum subsided more rapidly than in the emission lines. Although our time resolution was limited, in our brightest flare we saw flux in the continuum clearly peaking before flux in the emission lines. We observed a progressive decrease in flare energy from H\b{eta} to H{\delta}. On average we found 37% of B band flare energy appeared in the H\b{eta} to H{\epsilon} emission lines with the remainder contributing to a rise in continuum flux. We measured black-body temperatures for the brightest flares between 10,500 +- 700 K and 19,500 +- 500 K and found a linear relationship between flare temperature and continuum flux at 4170 {\AA}. Balmer lines in flare-only spectra were well fitted by Gaussian profiles with some evidence of additional short-lived blue-shifted emission at the flare peak.Comment: 12 pages, 13 figures, accepted for publication in the Journal of the AAVS