Abstract:
This is the first study to show that cigarette smoking induced the LKB1/PEA 3/ΔNp63-dependent transcriptional regulation of inflammatory molecules, such as COX-2/PTGS-2. Using mainstream smoke extract (MSE) and sidestream smoke extract (SSE) as modeling tools for primary and secondhand smoking, we found that both MSE and SSE downregulated protein levels for LKB1, while upregulated protein levels for PEA 3 and COX-2 in a dose-dependent manner. Using the endogenous ChIP analysis, we further found that the C/EBPβ, NFκB, NF-Y (CHOP), PEA 3 (ETS) and ΔNp63 proteins bound to the specific area (-550 to -130) of the COX-2 promoter, while forming multiple protein complexes in lung cancer cells exposed to MSE and SSE. Our results define a novel link between various transcription factors occupying the COX-2 promoter and cellular response to cigarette smoke exposure bringing a new component, ΔNp63α, showing a critical role for cooperation between various chromatin components in regulation of COX-2 expression and, therefore strengthening the central role of inflammatory process in tumorigenesis of epithelial cells, especially after cigarette smoke exposure (both primary and secondhand).

Abstract:
This is the first study to show that cigarette smoking induced the LKB1/PEA 3/ΔNp63-dependent transcriptional regulation of inflammatory molecules, such as COX-2/PTGS-2. Using mainstream smoke extract (MSE) and sidestream smoke extract (SSE) as modeling tools for primary and secondhand smoking, we found that both MSE and SSE downregulated protein levels for LKB1, while upregulated protein levels for PEA 3 and COX-2 in a dose-dependent manner. Using the endogenous ChIP analysis, we further found that the C/EBPβ, NFκB, NF-Y (CHOP), PEA 3 (ETS) and ΔNp63 proteins bound to the specific area (-550 to -130) of the COX-2 promoter, while forming multiple protein complexes in lung cancer cells exposed to MSE and SSE. Our results define a novel link between various transcription factors occupying the COX-2 promoter and cellular response to cigarette smoke exposure bringing a new component, ΔNp63α, showing a critical role for cooperation between various chromatin components in regulation of COX-2 expression and, therefore strengthening the central role of inflammatory process in tumorigenesis of epithelial cells, especially after cigarette smoke exposure (both primary and secondhand).

Abstract:
Aerobic glycolysis and mitochondrial dysfunction are common features of aggressive cancer growth. We observed promoter methylation and loss of expression in neurofilament heavy polypeptide (NEFH) in a significant proportion of primary esophageal squamous cell carcinoma (ESCC) samples that were of a high tumor grade and advanced stage. RNA interference-mediated knockdown of NEFH accelerated ESCC cell growth in culture and increased tumorigenicity in vivo, whereas forced expression of NEFH significantly inhibited cell growth and colony formation. Loss of NEFH caused up-regulation of pyruvate kinase-M2 type and down-regulation of pyruvate dehydrogenase, via activation of the Akt/β-catenin pathway, resulting in enhanced aerobic glycolysis and mitochondrial dysfunction. The acceleration of glycolysis and mitochondrial dysfunction in NEFH-knockdown cells was suppressed in the absence of β-catenin expression, and was decreased by the treatment of 2-Deoxyglucose, a glycolytic inhibitor, or API-2, an Akt inhibitor. Loss of NEFH activates the Akt/β-catenin pathway and increases glycolysis and mitochondrial dysfunction. Cancer cells with methylated NEFH can be targeted for destruction with specific inhibitors of deregulated downstream pathways.

Abstract:
Previous research in cold atmospheric plasma (CAP) and cancer cell interaction has repeatedly proven that the cold plasma induced cell death. It is postulated that the reactive oxygen species (ROS) and reactive nitrogen species (RNS) play a major role in the CAP cancer therapy. In this paper, we seek to determine a mechanism of CAP therapy on glioblastoma cells (U87) through an understanding of the composition of the plasma, including treatment time, voltage, flow-rate and plasma-gas composition. In order to determine the threshold of plasma treatment on U87, normal human astrocytes (E6/E7) were used as the comparison cell line. Our data showed that the 30 sec plasma treatment caused 3-fold cell death in the U87 cells compared to the E6/E7 cells. All the other compositions of cold plasma were performed based on this result: plasma treatment time was maintained at 30 s per well while other plasma characteristics such as voltage, flow rate of source gas, and composition of source gas were changed one at a time to vary the intensity of the reactive species composition in the plasma jet, which may finally have various effect on cells reflected by cell viability. We defined a term “plasma dosage” to summarize the relationship of all the characteristics and cell viability.

Abstract:
A force with an acceleration that is equal to multiples greater than the speed of light per unit time is exerted on a cloud of charged particles. The particles are resultantly accelerated to within an infinitesimal fraction of the speed of light. As the force or acceleration increases, the particles’ velocity asymptotically approaches but never achieves the speed of light obeying relativity. The asymptotic increase in the particles’ velocity toward the speed of light as acceleration increasingly surpasses the speed of light per unit time does not compensate for the momentum value produced on the particles at sub-light velocities. Hence, the particles’ inertial mass value must increase as acceleration increases. This increase in the particles’ inertial mass as the particles are accelerated produce a gravitational field which is believed to occur in the oscillation of quarks achieving velocities close to the speed of light. The increased inertial mass of the density of accelerated charged particles becomes the source mass (or Big “M”) in Newton’s equation for gravitational force. This implies that a space-time curve is generated by the accelerated particles. Thus, it is shown that the acceleration number (or multiple of the speed of light greater than 1 per unit of time) and the number of charged particles in the cloud density are surjectively mapped to points on a differential manifold or space-time curved surface. Two aspects of Einstein’s field equations are used to describe the correspondence between the gravitational field produced by the accelerated particles and the resultant space-time curve. The two aspects are the Schwarzchild metric and the stress energy tensor. Lastly, the possibility of producing a sufficient acceleration or electromagnetic force on the charged particles to produce a gravitational field is shown through the Lorentz force equation. Moreover, it is shown that a sufficient voltage can be generated to produce an acceleration/force on the particles that is multiples greater than the speed of light per unit time thereby generating gravity.

Abstract:
Cosmological expansion or inflation is mathematically described by the theoretical notion of inverse gravity whose variations are parameterized by a factor that is a function of the distance to which cosmological expansion takes prominence over gravity. This assertion is referred to as the inverse gravity inflationary assertion. Thus, a correction to Newtonian gravitational force is introduced where a parameterized inverse gravity force term is incorporated into the classical Newtonian gravitational force equation where the inverse force term is negligible for distances less than the distance to which cosmological expansion takes prominence over gravity. Conversely, at distances greater than the distance to which cosmological expansion takes prominence over gravity. The inverse gravity term is shown to be dominant generating universal inflation. Gravitational potential energy is thence defined by the integral of the difference (or subtraction) between the conventional Newtonian gravitational force term and the inverse gravity term with respect to radius (r) which allows the formulation, incorporation, and mathematical description to and of gravitational redshift, the Walker-Robertson scale factor, the Robinson-Walker metric, the Klein-Gordon lagrangian, and dark energy and its relationship to the energy of the big bang in terms of the Inverse gravity inflationary assertion. Moreover, the dynamic pressure of the expansion of a cosmological fluid in a homogeneous isotropic universe is mathematically described in terms of the inverse gravity inflationary assertion using the stress-energy tensor for a perfect fluid. Lastly, Einstein’s field equations for the description of an isotropic and homogeneous universe are derived incorporating the mathematics of the inverse gravity inflationary assertion to fully show that the theoretical concept is potentially interwoven into the cosmological structure of the universe.

Abstract:
Phosphorylation has been shown to have a significant impact on expanded huntingtin-mediated cellular toxicity. Several phosphorylation sites have been identified on the huntingtin (Htt) protein. To find new potential therapeutic targets for Huntington's Disease (HD), we used mass spectrometry to identify novel phosphorylation sites on N-terminal Htt, expressed in HEK293 cells. Using site-directed mutagenesis we introduced alterations of phosphorylation sites in a N586 Htt construct containing 82 polyglutamine repeats. The effects of these alterations on expanded Htt toxicity were evaluated in primary neurons using a nuclear condensation assay and a direct time-lapse imaging of neuronal death. As a result of these studies, we identified several novel phosphorylation sites, validated several known sites, and discovered one phospho-null alteration, S116A, that had a protective effect against expanded polyglutamine-mediated cellular toxicity. The results suggest that S116 is a potential therapeutic target, and indicate that our screening method is useful for identifying candidate phosphorylation sites.

Abstract:
The observed basic weather variables are the main
representative of climate trends and the atmosphere. The unresolved
meteorological scale in weather observation such as micro scale, can produce a
noticeable bias in amplitude, frequency, phase and climate trend of each
observed variable time series. The bias in climate trend due to a small scale
eddy can be as high as the amplitude of the eddy which could be greater than 1°C in a temperature trend. Such biased
measurements of the state of the atmosphere limit all climate related studies.

The burrowing and feeding activities
of earthworms may have a strong effect on the flux of N_{2}O from
agricultural soils. As such, shifts to agricultural management practices that
increase the number of earthworms require an understanding of the role of
earthworms in N_{2}O dynamics. We conducted a field experiment to
examine the effects of addition of anecic earthworms (Lumbricus terrestris) on N_{2}O flux in a field previously
planted with corn (Zea mays) in
southern Rhode Island, USA. Plots were
amended with (^{15}NH_{4})_{2}SO_{4} and either
0 (CTL) or 48 L. terrestris m^{-2} (EW). The flux of N_{2}O, ^{15}N_{2}O
and ^{15}N_{2 }was measured over 28 days between October and
November 2008. The EW treatment had a significantly higher flux of N_{2}O
and ^{15}N_{2}O 1-3 days after ^{15}NH_{4} addition. No treatment effects were observed on ^{15}N_{2} flux. The addition of earthworms significantly increased (Day 1) and decreased
(Day 12) the mole fraction of N_{2}O relative to the CTL. Our results
suggest that anecic earthworm additions can increase N_{2}O flux from
inorganic fertilizer N amendments, but the effects appear to short-lived.

Abstract:
Laurel wilt (LW) is a lethal disease of trees in the
Lauraceae plant family, including the economic significant commercial crop
avocado, Persea americana. To date,
an estimated one-half billion native trees have been destroyed by the disease
in the southeastern United States, including the loss of significant and
diverse taxa in the Everglades. In the US state of Florida, laurel wilt has
spread rapidly throughout the South Florida commercial avocado production area.
Since its arrival in 2011, LW has been responsible for the death of about 7000
trees or 1% of the production area. Given the destructive nature of this
disease, there are major concerns over the future of the Florida avocado
industry. Cost-effective management of LW remains an elusive goal, and current
recommendations rely heavily on the early detection and destruction of affected
trees (sanitation) in an effort to slow the spread of the disease. An empirical
economic model is used to determine when all trees in an orchard affected by LW
would need to be destroyed due to negative net returns.