Investigating prostate cancer tumour-stroma interactions - clinical and biological insights from an evolutionary game

BACKGROUND: Tumours are made up of a mixed population of different types of cells that include normal structures as well as ones associated with the malignancy, and there are multiple interactions between the malignant cells and the local microenvironment. These intercellular interactions, modulated by the microenvironment, effect tumour progression and represent a largely under appreciated therapeutic target. We use observations of primary tumor biology from prostate cancer to extrapolate a mathematical model: specifically; it has been observed that in prostate cancer three disparate cellular outcomes predominate: (i) the tumour remains well differentiated and clinically indolent - in this case the local stromal cells may act to restrain the growth of the cancer; (ii) early in its genesis the tumour acquires a highly malignant phenotype, growing rapidly and displacing the original stromal population (often referred to as small cell prostate cancer) - these less common aggressive tumours are relatively independent of the local microenvironment; and, (iii) the tumour co-opts the local stroma - taking on a classic stromagenic phenotype where interactions with the local microenvironment are critical to the cancer growth. METHODS: We present an evolutionary game theoretical construct that models the influence of tumour-stroma interactions in driving these outcomes. We consider three characteristic and distinct cellular populations: stromal cells, tumour cells that are self-reliant in terms of microenvironmental factors and tumour cells that depend on the environment for resources but can also co-opt stroma. 
RESULTS: Using evolutionary game theory we explore a number of different scenarios that elucidate the impact of tumour-stromal interactions on the dynamics of prostate cancer growth and progression and how different treatments in the metastatic setting can affect different types of tumors.
CONCLUSIONS: The tumour microenvironment plays a crucial role selecting the traits of the tumour cells that will determine prostate cancer progression. Equally important, treatments like hormone therapy affect the selection of these cancer phenotypes making it very important to understand how they impact prostate cancer’s somatic evolution

NIR spectroscopy of the Sun and HD20010 - Compiling a new linelist in the NIR

Context: Effective temperature, surface gravity, and metallicity are basic spectroscopic stellar parameters necessary to characterize a star or a planetary system. Reliable atmospheric parameters for FGK stars have been obtained mostly from methods that relay on high resolution and high signal-to-noise optical spectroscopy. The advent of a new generation of high resolution near-IR spectrographs opens the possibility of using classic spectroscopic methods with high resolution and high signal-to-noise in the NIR spectral window. Aims: We aim to compile a new iron line list in the NIR from a solar spectrum to derive precise stellar atmospheric parameters, comparable to the ones already obtained from high resolution optical spectra. The spectral range covers 10 000 {\AA} to 25 000 {\AA}, which is equivalent to the Y, J, H, and K bands. Methods: Our spectroscopic analysis is based on the iron excitation and ionization balance done in LTE. We use a high resolution and high signal-to-noise ratio spectrum of the Sun from the Kitt Peak telescope as a starting point to compile the iron line list. The oscillator strengths (log gf) of the iron lines were calibrated for the Sun. The abundance analysis was done using the MOOG code after measuring equivalent widths of 357 solar iron lines. Results: We successfully derived stellar atmospheric parameters for the Sun. Furthermore, we analysed HD20010, a F8IV star, from which we derived stellar atmospheric parameters using the same line list as for the Sun. The spectrum was obtained from the CRIRES- POP database. The results are compatible with the ones found in the literature, confirming the reliability of our line list. However, due to the quality of the data we obtain large errors.Comment: 9 pages and 9 figure

Nuclear shadowing from exclusive quarkonium photoproduction at the BNL RHIC and CERN LHC

The photonuclear production of vector mesons in ultraperipheral heavy ion collisions is investigated within the collinear approach using different parameterizations for the nuclear gluon distribution. The integrated cross section and the rapidity distribution for the $AA \to V AA$ ($V = J/\Psi, \Upsilon$) process are computed for energies of RHIC and LHC. A comparison with the recent PHENIX data on coherent production of $J/\Psi$ mesons is also presented. We demonstrate that the study of the exclusive quarkonium photoproduction can be used to constrain the nuclear effects in the gluon distribution.Comment: 8 pages, 4 figures, 2 tables. Version to be published in Physical Review

Pion propagation in the linear sigma model at finite temperature

We construct effective one-loop vertices and propagators in the linear sigma model at finite temperature, satisfying the chiral Ward identities and thus respecting chiral symmetry, treating the pion momentum, pion mass and temperature as small compared to the sigma mass. We use these objects to compute the two-loop pion self-energy. We find that the perturbative behavior of physical quantities, such as the temperature dependence of the pion mass, is well defined in this kinematical regime in terms of the parameter m_pi^2/4pi^2f_pi^2 and show that an expansion in terms of this reproduces the dispersion curve obtained by means of chiral perturbation theory at leading order. The temperature dependence of the pion mass is such that the first and second order corrections in the above parameter have the same sign. We also study pion damping both in the elastic and inelastic channels to this order and compute the mean free path and mean collision time for a pion traveling in the medium before forming a sigma resonance and find a very good agreement with the result from chiral perturbation theory when using a value for the sigma mass of 600 MeV.Comment: 18 pages, 11 figures, uses RevTeX and epsfig. Expanded conclusions, added references. To appear in Phys. Rev.

Fermion scattering off electroweak phase transition kink walls with hypermagnetic fields

We study the scattering of fermions off a finite width kink wall during the electroweak phase transition in the presence of a background hypermagnetic field. We derive and solve the Dirac equation for such fermions and compute the reflection and transmission coefficients for the case when the fermions move from the symmetric to the broken symmetry phase. We show that the chiral nature of the fermion coupling with the background field in the symmetric phase generates an axial asymmetry in the scattering processes. We discuss possible implications of such axial charge segregation for baryon number generation.Comment: 9 pages, 3 Postscript figures, uses RevTeX4. Expanded discussion, published versio

Heat shock-induced phosphorylation of TAR DNA-binding protein 43 (TDP-43) by MAPK/ERK kinase regulates TDP-43 function

TAR DNA-binding protein (TDP-43) is a highly conserved and essential DNA- and RNA-binding protein that controls gene expression through RNA processing, in particular, regulation of splicing. Intracellular aggregation of TDP-43 is a hallmark of amyotrophic lateral sclerosis and ubiquitin-positive frontotemporal lobar degeneration. This TDP-43 pathology is also present in other types of neurodegeneration including Alzheimer's disease. We report here that TDP-43 is a substrate of MEK, a central kinase in the MAPK/ERK signaling pathway. TDP-43 dual phosphorylation by MEK, at threonine 153 and tyrosine 155 (p-T153/Y155), was dramatically increased by the heat shock response (HSR) in human cells. HSR promotes cell survival under proteotoxic conditions by maintaining protein homeostasis and preventing protein misfolding. MEK is activated by HSR and contributes to the regulation of proteome stability. Phosphorylated TDP-43 was not associated with TDP-43 aggregation, and p-T153/Y155 remained soluble under conditions that promote protein misfolding. We found that active MEK significantly alters TDP-43-regulated splicing and that phosphomimetic substitutions at these two residues reduce binding to GU-rich RNA. Cellular imaging using a phospho-specific p-T153/Y155 antibody showed that phosphorylated TDP-43 was specifically recruited to the nucleoli, suggesting that p-T153/Y155 regulates a previously unappreciated function of TDP-43 in the processing of nucleolar-associated RNA. These findings highlight a new mechanism that regulates TDP-43 function and homeostasis through phosphorylation and, therefore, may contribute to the development of strategies to prevent TDP-43 aggregation and to uncover previously unexplored roles of TDP-43 in cell metabolism