Analysis of RANK-c interaction partners identifies TRAF3 as a critical regulator of breast cancer aggressiveness.

Breast cancer is a highly heterogeneous disease both at the histological and molecular levels. We have previously shown that RANK-c is a regulator of NF-κB signaling and exerts a suppressive effect on aggressive properties of ER negative breast cancer cells, while there is an opposite effect on ER positive cell lines. In order to identify molecular determinants that govern the opposing function of RANK-c in breast cancer cells we employed the two cell lines with the highest degree of phenotypic divergence upon RANK-c-expression (SKBR3 and BT474) and identified proteins that interact with RANK-c by affinity-enrichment mass spectrometry (AE-MS) analysis.

Coarse-Grained Model Incorporating Short- and Long-Range Effective Potentials for the Fast Simulation of Micelle Formation in Solutions of Ionic Surfactants.

A coarse-grained model comprising short- and long-range effective potentials, parametrized with the iterative Boltzmann inversion (IBI) method, is presented for capturing micelle formation in aqueous solutions of ionic surfactants using as a model system sodium dodecyl sulfate (SDS). In the coarse-grained (CG) model, each SDS molecule is represented as a sequence of four beads while each water molecule is modeled as a single bead. The proposed CG scheme involves ten potential energy functions: four of them describe bonded interactions and control the distribution functions of intramolecular degrees of freedom (bond lengths, valence angles, and dihedrals) along an SDS molecule while the other six account for intermolecular interactions between pairs of SDS and water beads and control the radial distribution functions.

Cellular Senescence in Normal Mammary Gland and Breast Cancer. Implications for Cancer Therapy.

Cellular senescence (CS) is a major homeostatic biological process, which plays a key role in normal tissue development and provides protection from stressful cell insults. The role of CS in mammary-gland development and breast cancer is not well understood. While there is a lack of experimental data on the role of CS in the development of the pre-pubertal mammary gland, there is evidence for a biphasic senescence response in adult normal-mammary-epithelial cells, where the bypass of the first senescence barrier (M0) seems to be a key step in the development of premalignant lesions, with genetic abnormalities that resemble in situ breast carcinoma.

The phase behaviour of cetyltrimethylammonium chloride surfactant aqueous solutions at high concentrations: an all-atom molecular dynamics simulation study.

We explore the phase behaviour of aqueous solutions of the cetyltrimethyl ammonium chloride (CTAC) surfactant and in particular the transition from the micellar phase (L) to the hexagonal columnar phase (H) by employing all-atom (AA) molecular dynamics (MD) simulations for six CTAC concentrations in the range of 34.1 wt% to 70.5 wt%, at the temperature of 318 K and pressure of 1 atm.

Field-induced anti-nematic and biaxial ordering in binary mixtures of discotic mesogens and spherical magnetic nanoparticles.

Using computer simulations we explore the equilibrium structure and response to external stimuli of complex magnetic hybrids consisting of magnetic particles in discotic liquid crystalline matrices. We show that the anisotropy of the liquid crystalline matrix (either in the nematic or in the columnar phase) promotes the collective orientational ordering of self-assembled magnetic particles. Upon applying an external homogeneous magnetic field in an otherwise isotropic state, the magnetic particles self-assemble into linear-rodlike-chains.

Quantitative Prediction of the Structure and Viscosity of Aqueous Micellar Solutions of Ionic Surfactants: A Combined Approach Based on Coarse-Grained MARTINI Simulations Followed by Reverse-Mapped All-Atom Molecular Dynamics Simulations.

We address the problem of the quantitative prediction of micelle formation in dilute aqueous solutions of ionic surfactants using sodium dodecyl sulfate (SDS) as a model system through a computational approach that involves three steps: (a) execution of coarse-grained simulations based on the MARTINI force field (with slightly modified parameters to afford the formation of large micelles); (b) reverse mapping of the final self-assembled coarse-grained configuration into an all-atom configuration; and (c) final relaxation of this all-atom configuration through short-time (on the order of a few tens of nanoseconds), detailed isothermal-isobaric molecular dynamics simulations using the CHARMM36 force field. For a given concentration of the solution in SDS molecules, the modified MARTINI-based coarse-grained simulations lead to the formation of large micelles characterized by mean aggregation numbers above the experimentally observed ones. However, by reintroducing the detailed chemical structure through a strategy that solves a well-defined geometric problem and re-equilibrating, these large micellar aggregates quickly dissolve to smaller ones and equilibrate to sizes that perfectly match the average micelle size measured experimentally at the given surfactant concentration.

Molecular simulation of the high temperature phase behaviour of α-unsubstituted sexithiophene.

We examine the high-temperature phase behaviour of α-unsubstituted sexithiophene (α-6T) by means of Molecular Dynamics (MD) and Monte Carlo (MC) simulations using a recently developed state-of-the-art algorithm based on internal bridging moves. In the MD simulations, a realistic fully flexible united-atom model is used. In the MC simulations, a stiffer version of this united-atom model is implemented by restricting atoms on thiophene rings to remain strictly co-planar by employing holonomic constraints for all bond lengths and intra-ring bond bending angles; on the other hand, inter-ring torsion and bond bending angles are considered to be fully flexible subject to suitable potential energy functions.

Orientational order and translational dynamics of magnetic particle assemblies in liquid crystals.

Implementing extensive molecular dynamics simulations we explore the organization of magnetic particle assemblies (clusters) in a uniaxial liquid crystalline matrix comprised of rodlike particles. The magnetic particles are modelled as soft dipolar spheres with diameter significantly smaller than the width of the rods. Depending on the dipolar strength coupling the magnetic particles arrange into head-to-tail configurations forming various types of clusters including rings (closed loops) and chains.

Colloidal Suspensions of Rodlike Nanocrystals and Magnetic Spheres under an External Magnetic Stimulus: Experiment and Molecular Dynamics Simulation.

Using experiments and molecular dynamics simulations, we explore magnetic field-induced phase transformations in suspensions of nonmagnetic rodlike and magnetic sphere-shaped particles. We experimentally demonstrate that an external uniform magnetic field causes the formation of small, stable clusters of magnetic particles that, in turn, induce and control the orientational order of the nonmagnetic subphase. Optical birefringence was studied as a function of the magnetic field and the volume fractions of each particle type.

Utilization of Systemic Chemotherapy in Advanced Urothelial Cancer: A Retrospective Collaborative Study by the Hellenic Genitourinary Cancer Group (HGUCG).

Background: Advanced urothelial cancer (AUCa) is associated with poor long-term survival. Two major concerns are related to nonexposure to cisplatin-based chemotherapy and poor outcome after relapse. Our purpose was to record patterns of practice in AUCa in Greece, focusing on first-line treatment and management of relapsed disease.

Treatment of relapsed urothelial bladder cancer with vinflunine: real-world evidence by the Hellenic Genitourinary Cancer Group.

Relapsed urothelial cancer represents an unmet medical need. Vinflunine is a third-generation antimicrotubuline inhibitor and is currently the only approved drug for second-line treatment across the European Union. We conducted a retrospective analysis assessing the efficacy and safety of vinflunine in 71 Greek patients with relapsed urothelial cancer who were treated between 2005 and 2014.

Spontaneous ordering of magnetic particles in liquid crystals: From chains to biaxial lamellae.

Using Monte Carlo computer simulations we explore the self-assembly and ordering behavior of a hybrid, soft magnetic system consisting of small magnetic nanospheres in a liquid-crystalline (LC) matrix. Inspired by recent experiments with colloidal rod matrices, we focus on conditions where the sphere and rod diameters are comparable. Already in the absence of a magnetic field, the nematic ordering of the LC can stabilize the formation of magnetic chains along the nematic or smectic director, yielding a state with local (yet no macroscopic) magnetic order.

Molecular simulation study of polar order in orthogonal bent-core smectic liquid crystals.

We explore the phase behavior and structure of orthogonal smectic liquid crystals consisting of bent-core molecules (BCMs) by means of Monte Carlo molecular simulations. A simple athermal molecular model is introduced that describes the basic features of the BCMs. Phase transitions between uniaxial and biaxial (antiferroelectric) orthogonal smectics are obtained.

Tunable structures of mixtures of magnetic particles in liquid-crystalline matrices.

We investigate the self-organization of a binary mixture of similar sized rods and dipolar soft spheres by means of Monte-Carlo simulations. We model interparticle interactions by employing anisotropic Gay-Berne, dipolar and soft-sphere interactions. In the limit of vanishing magnetic moments we obtain a variety of fully miscible liquid crystalline phases including nematic, smectic and lamellar phases.

Ulcerative colitis six years after colon cancer: only a coincidence?

The association between inflammatory bowel disease and colorectal cancer is well known. Ulcerative colitis is a risk factor for the development of colorectal cancer, and this risk increases with the activity and duration of bowel inflammation. Here we describe the case of a 52-year-old man who developed ulcerative colitis 6 years after the diagnosis and treatment of colon cancer.

Biaxial mesophase behavior of amphiphilic anisometric colloids: a simulation study.

The phase behavior of amphiphilic anisometric particles is explored using Monte Carlo simulations. The particles are composed of two incompatible laterally attached units: a spherocylinder and a spheroplatelet. A liquid crystalline phase polymorphism is obtained including biaxial nematic, (quasi long range biaxial) calamitic smectic-A, biaxial lamellar and columnar phases.

Supramolecular nature of the nematic-nematic phase transitions of hard boardlike molecules.

The phase behavior of hard boardlike biaxial particles of relative dimensions close to the clamitic to discotic crossover is explored by means of Monte Carlo molecular simulations. Transitions between two distinct biaxial nematic phases as well as transitions from a biaxial nematic to a uniaxial Sm-A phase are obtained. The formation of anisotropic supramolecular assemblies is demonstrated and is quantified by means of rotationally invariant pair correlation functions.

Molecular simulation of hierarchical structures in bent-core nematic liquid crystals.

The structure of nematic liquid crystals formed by bent-core mesogens (BCMs) is studied in the context of Monte Carlo simulations of a simple molecular model that captures the symmetry, shape, and flexibility of achiral BCMs. The results indicate the formation of (i) clusters exhibiting local smectic order, orthogonal or tilted, with strong in-layer polar correlations and antiferroelectric juxtaposition of successive layers and (ii) large homochiral domains through the helical arrangement of the tilted smectic clusters, while the orthogonal clusters produce achiral (untwisted) nematic states.

Molecular modeling of liquid crystalline self-organization of fullerodendrimers: columnar to lamellar phase transitions driven by temperature and/or concentration changes.

The molecular cubic-block model [ J. Chem. Phys.

Self-organisation of fullerene-containing conical supermesogens.

A molecular model of cubic building blocks is used to describe the mesomorphism of conical fullerenomesogens. Calculations based on density functional molecular theory and on Monte Carlo computer simulations give qualitatively similar results that are also in good agreement with the experimentally observed mesomorphic behaviour. The columnar and lamellar mesophases obtained are non-polar, and their relative stability is controlled by a single model parameter representing the softness of the repulsive interactions among the building blocks of the conical molecules.