Decomposition Analyses Applied to a Complex Ultradian Biorhythm: The Oscillating NADH Oxidase Activity of Plasma Membranes Having a Potential Time-Keeping (Clock) Function

Seasonal decomposition analyses were applied to the statistical evaluation of an oscillating activity for a plasma membrane NADH oxidase activity with a temperature compensated period of 24 min. The decomposition fits were used to validate the cyclic oscillatory pattern. Three measured values, average percentage error (MAPE), a measure of the periodic oscillation, mean average deviation (MAD), a measure of the absolute average deviations from the fitted values, and mean standard deviation (MSD), the measure of standard deviation from the fitted values plus R-squared and the Henriksson-Merton p value were used to evaluate accuracy. Decomposition was carried out by fitting a trend line to the data, then detrending the data if necessary, by subtracting the trend component. The data, with or without detrending, were then smoothed by subtracting a centered moving average of length equal to the period length determined by Fourier analysis. Finally, the time series were decomposed into cyclic and error components. The findings not only validate the periodic nature of the major oscillations but suggest, as well, that the minor intervening fluctuations also recur within each period with a reproducible pattern of recurrence. biological clockdecomposition analysesultradian rhythmtemperature compensationcircadian rhythmcultured cells

Broad targeting of resistance to apoptosis in cancer

Apoptosis or programmed cell death is natural way of removing aged cells from the body. Most of the anti-cancer therapies trigger apoptosis induction and related cell death networks to eliminate malignant cells. However, in cancer, de-regulated apoptotic signaling, particularly the activation of an anti-apoptotic systems, allows cancer cells to escape this program leading to uncontrolled proliferation resulting in tumor survival, therapeutic resistance and recurrence of cancer. This resistance is a complicated phenomenon that emanates from the interactions of various molecules and signaling pathways. In this comprehensive review we discuss the various factors contributing to apoptosis resistance in cancers. The key resistance targets that are discussed include (1) Bcl-2 and Mcl-1 proteins; (2) autophagy processes; (3) necrosis and necroptosis; (4) heat shock protein signaling; (5) the proteasome pathway; (6) epigenetic mechanisms; and (7) aberrant nuclear export signaling. The shortcomings of current therapeutic modalities are highlighted and a broad spectrum strategy using approaches including (a) gossypol; (b) epigallocatechin-3-gallate; (c) UMI-77 (d) triptolide and (e) selinexor that can be used to overcome cell death resistance is presented. This review provides a roadmap for the design of successful anti-cancer strategies that overcome resistance to apoptosis for better therapeutic outcome in patients with cancer

Creation of a Committed Johnsongrass Area and Implementation Study

This project was to develop a committed roadside Johnson grass research area with controlled mowing and date of spraying adjacent to US 63 from I 74 south to JCT US 36 and to continue studies of a cold-adapted Johnson grass ecotype identified in the Northern-most tier counties in Indiana in an area adjacent to IN 23 between South Bend and New Liberty, IN. The cold-adapted Johnson grass provides a further threat of encroachment of roadside-established Johnson grass onto adjacent cropland of considerable potential economic consequence. Completed was a 3-year study with Roundup alone and in combination with Outrider either as a tank mix or sequentially with Roundup followed after several weeks by Outrider or Outrider followed after several weeks by Roundup comparing different rates, dates of application and stages of development. Roundup alone or in sequence several weeks following Outrider was without effect on Johnson grass regrowth. A small benefit from 0.4 lb/A Roundup 3 to 6 weeks post Outrider was insufficient to justify the additional cost and offered no benefit over post Outrider mowing at the same stage. Correlations were with stage of growth with Johnson grass 24 to 30” tall, 33-36” tall and 40-42” tall without seed heads, seed heads forming in the boot, early anthesis (flowering), late flowering or with seed heads formed and 50-60” tall and spray date. Fall 2006 marked initiation of the final implementation of the project. Outrider alone at a rate of 0.5 oz/100 gal plus a detergent at 0.12% of the total spray mixture spot sprayed to the point of runoff is to be recommended. Best results are expected with regrowth following mowing although about \u3e90% control can be expected from midseason to late spraying of mature Johnson grass. Evaluated in 2007 and 2008 was the optimum regrowth stage to treat and the response to mowing following spraying. Johnson grass can be mowed very soon after spraying (next day or late same day) without loss of treatment effectiveness. In laboratory studies, a candidate Outrider binding protein was identified and cloned

A Gravity-Responsive Time-Keeping Protein of the Plant and Animal Cell Surface

The hypothesis under investigation was that a ubiquinol (NADH) oxidase protein of the cell surface with protein disulfide-thiol interchange activity (= NOX protein) is a plant and animal time-keeping ultradian (period of less than 24 h) driver of both cell enlargement and the biological clock that responds to gravity. Despite considerable work in a large number of laboratories spanning several decades, this is, to my knowledge, our work is the first demonstration of a time-keeping biochemical reaction that is both gravity-responsive and growth-related and that has been shown to determine circadian periodicity. As such, the NOX protein may represent both the long-sought biological gravity receptor and the core oscillator of the cellular biological clock. Completed studies have resulted in 12 publications and two issued NASA-owned patents of the clock activity. The gravity response and autoentrainment were characterized in cultured mammalian cells and in two plant systems together with entrainment by light and small molecules (melatonin). The molecular basis of the oscillatory behavior was investigated using spectroscopic methods (Fourier transform infrared and circular dichroism) and high resolution electron microscopy. We have also applied these findings to an understanding of the response to hypergravity. Statistical methods for analysis of time series phenomena were developed (Foster et al., 2003)