Assessment of viral and non-viral gene transfer into adult rat brains using HSV-1, calcium phosphate and PEI-based methods

CNS gene transfer could provide new approaches to the modelling of neurodegenerative diseases and devising potential therapies. One such disorder is Parkinson’s disease (PD), in which dysfunction of several different metabolic processes has been implicated. Here we review the literature on gene transfer systems based on herpes simplex virus type 1 (HSV-1) and non-viral polyethyleneimine (PEI) and calcium phosphate nanoparticle methods. We also assess the usefulness of various CNS gene delivery methods and present some of our own data to exemplify such usefulness. Our data result from vectors stereotaxically introduced to the substantia nigra (SN) of adult rats and evaluated 1 week and/or 1 month post injection using histochemical methods to assess recombinant ß-galactosidase enzyme activity. Gene transfer using PEI or calcium phosphate-mediated transfections was observed for both methods and PEI was comparable to that of HSV-1 amplicon. Our data show that the amplicon delivery was markedly increased when packaged with a helper virus and was similar to the expression profile achieved with a full-size replication-defective HSV-1 recombinant (8117/43). We also examine whether PEI or HSV-1 amplicon-mediated gene transfer could facilitate assessment of the biological effects induced by a dominant negative FGF receptor-1 mutant to model the reduced FGF signalling thought to occur in Parkinson’s disease

Can dark matter be a Bose-Einstein condensate?

We consider the possibility that the dark matter, which is required to explain the dynamics of the neutral hydrogen clouds at large distances from the galactic center, could be in the form of a Bose-Einstein condensate. To study the condensate we use the non-relativistic Gross-Pitaevskii equation. By introducing the Madelung representation of the wave function, we formulate the dynamics of the system in terms of the continuity equation and of the hydrodynamic Euler equations. Hence dark matter can be described as a non-relativistic, Newtonian Bose-Einstein gravitational condensate gas, whose density and pressure are related by a barotropic equation of state. In the case of a condensate with quartic non-linearity, the equation of state is polytropic with index $n=1$. To test the validity of the model we fit the Newtonian tangential velocity equation of the model with a sample of rotation curves of low surface brightness and dwarf galaxies, respectively. We find a very good agreement between the theoretical rotation curves and the observational data for the low surface brightness galaxies. The deflection of photons passing through the dark matter halos is also analyzed, and the bending angle of light is computed. The bending angle obtained for the Bose-Einstein condensate is larger than that predicted by standard general relativistic and dark matter models. Therefore the study of the light deflection by galaxies and the gravitational lensing could discriminate between the Bose-Einstein condensate dark matter model and other dark matter models.Comment: 20 pages, 7 figures, accepted for publication in JCAP, references adde

HMG1A and PPARG are differently expressed in the liver of fat and lean broilers

The expression of nine functional candidates for QT abdominal fat weight and relative abdominal fat content was investigated by real-time polymerase chain reaction (PCR) in the liver, adipose tissue, colon, muscle, pituitary gland and brain of broilers. The high mobility group AT-hook 1 (HMG1A) gene was up-regulated in liver with a ratio of means of 2.90 (P ≤ 0.01) in the «fatty» group (relative abdominal fat content 3.5 ± 0.18%, abdominal fat weight 35.4 ± 6.09 g) relative to the «lean» group (relative abdominal fat content 1.9 ± 0.56%, abdominal fat weight 19.2 ± 5.06 g). Expression of this gene was highly correlated with the relative abdominal fat content (0.70, P ≤ 0.01) and abdominal fat weight (0.70, P ≤ 0.01). The peroxisome proliferator-activated receptor gamma (PPARG) gene was also up-regulated in the liver with a ratio of means of 3.34 (P ≤ 0.01) in the «fatty» group relative to the «lean» group. Correlation of its expression was significant with both the relative abdominal fat content (0.55, P ≤ 0.05) and the abdominal fat weight (0.57, P ≤ 0.01). These data suggest that the HMG1A and PPARG genes were candidate genes for abdominal fat deposition in chickens. Searching of rSNPs in regulatory regions of the HMG1A and PPARG genes could provide a tool for gene-assisted selection

Classical big-bounce cosmology: dynamical analysis of a homogeneous and irrotational Weyssenhoff fluid

A dynamical analysis of an effective homogeneous and irrotational Weyssenhoff fluid in general relativity is performed using the 1+3 covariant approach that enables the dynamics of the fluid to be determined without assuming any particular form for the space-time metric. The spin contributions to the field equations produce a bounce that averts an initial singularity, provided that the spin density exceeds the rate of shear. At later times, when the spin contribution can be neglected, a Weyssenhoff fluid reduces to a standard cosmological fluid in general relativity. Numerical solutions for the time evolution of the generalised scale factor in spatially-curved models are presented, some of which exhibit eternal oscillatory behaviour without any singularities. In spatially-flat models, analytical solutions for particular values of the equation-of-state parameter are derived. Although the scale factor of a Weyssenhoff fluid generically has a positive temporal curvature near a bounce, it requires unreasonable fine tuning of the equation-of-state parameter to produce a sufficiently extended period of inflation to fit the current observational data.Comment: 34 pages, 18 figure

Depletion-Driven Morphological Control of Bundled Actin Networks

The actin cytoskeleton is a semiflexible biopolymer network whose morphology is controlled by a wide range of biochemical and physical factors. Actin is known to undergo a phase transition from a single-filament state to a bundled state by the addition of polyethylene glycol (PEG) molecules in sufficient concentration. While the depletion interaction experienced by these biopolymers is well-known, the effect of changing the molecular weight of the depletant is less well understood. Here, we experimentally identify a phase transition in solutions of actin from networks of filaments to networks of bundles by varying the molecular weight of PEG polymers, while holding the concentration of these PEG polymers constant. We examine the states straddling the phase transition in terms of micro and macroscale properties. We find that the mesh size, bundle diameter, persistence length, and intra-bundle spacing between filaments across the line of criticality do not show significant differences, while the relaxation time, storage modulus, and degree of bundling change between the two states do show significant differences. Our results demonstrate the ability to tune actin network morphology and mechanics by controlling depletant size, a property which could be exploited to develop actin-based materials with switchable rigidity.Comment: 22 pages, 10 figures. Authors James Clarke and Francis Cavanna contributed equally; Changes: Added modeling work, extended dynamic light scattering analysi

Friction and wear properties of nano-Si<inf>3</inf>N<inf>4</inf>/nano-SiC composite under nanolubricated conditions

Friction and wear properties of nano-Si3N4/nano-SiC composite were studied under nanolubricated conditions. Mineral oil mixed with nanoparticles of diamond was used as lubricant. A friction coefficient of 0.043 and a wear coefficient of 4.2×10-7 were obtained for nano-Si3N4/nano-SiC composite under normal load of 600 N with mineral oil + 0.5 wt% nanodiamond, whereas a friction coefficient of 0.077 and a wear coefficient of 10.3×10-7 were obtained for nano-Si3N4/nano-SiC composite under normal load of 600 N with mineral oil. 3D surface profilometer was used to study the surface morphology of wear scars. Scanning electron microscopy (SEM) and X-ray diffraction (XRD) studies were conducted to illustrate reduction in friction and wear

Friction and wear phenomena of vegetable oil based lubricants with additives at severe sliding wear conditions

The tribological responses of palm oil and soybean oil, combined with two commercial antiwear additives (zinc dialkyl dithiophosphate and boron compound), were investigated at a lubricant temperature of 100 °C and under severe contact conditions in a reciprocating sliding contact. The friction coefficient of palm oil with zinc dialkyl dithiophosphate was closest to the commercial mineral engine oil, with a 2% difference. The soybean oil with zinc dialkyl dithiophosphate produced a 57% improvement in wear resistance compared to its pure oil state. The existence of boron nitride in vegetable oils was only responsive in reduction of wear rather than friction. The response of commercial antiwear additives with vegetable oils showed a potential for the future improvement in the performance of vegetable oils

Two-dimensional finite element simulation of fracture and fatigue behaviours of alumina microstructures for hip prosthesis

This paper describes a two-dimensional (2D) finite element simulation for fracture and fatigue behaviours of pure alumina microstructures such as those found at hip prostheses. Finite element models are developed using actual Al2O3 microstructures and a bilinear cohesive zone law. Simulation conditions are similar to those found at a slip zone in a dry contact between a femoral head and an acetabular cup of hip prosthesis. Contact stresses are imposed to generate cracks in the models. Magnitudes of imposed stresses are higher than those found at the microscopic scale. Effects of microstructures and contact stresses are investigated in terms of crack formation. In addition, fatigue behaviour of the microstructure is determined by performing simulations under cyclic loading conditions. It is shown that crack density observed in a microstructure increases with increasing magnitude of applied contact stress. Moreover, crack density increases linearly with respect to the number of fatigue cycles within a given contact stress range. Meanwhile, as applied contact stress increases, number of cycles to failure decreases gradually. Finally, this proposed finite element simulation offers an effective method for identifying fracture and fatigue behaviours of a microstructure provided that microstructure images are available

Coupled dark energy: Towards a general description of the dynamics

In dark energy models of scalar-field coupled to a barotropic perfect fluid, the existence of cosmological scaling solutions restricts the Lagrangian of the field \vp to p=X g(Xe^{\lambda \vp}), where X=-g^{\mu\nu} \partial_\mu \vp \partial_\nu \vp /2, $\lambda$ is a constant and $g$ is an arbitrary function. We derive general evolution equations in an autonomous form for this Lagrangian and investigate the stability of fixed points for several different dark energy models--(i) ordinary (phantom) field, (ii) dilatonic ghost condensate, and (iii) (phantom) tachyon. We find the existence of scalar-field dominant fixed points (\Omega_\vp=1) with an accelerated expansion in all models irrespective of the presence of the coupling $Q$ between dark energy and dark matter. These fixed points are always classically stable for a phantom field, implying that the universe is eventually dominated by the energy density of a scalar field if phantom is responsible for dark energy. When the equation of state w_\vp for the field \vp is larger than -1, we find that scaling solutions are stable if the scalar-field dominant solution is unstable, and vice versa. Therefore in this case the final attractor is either a scaling solution with constant \Omega_\vp satisfying 0<\Omega_\vp<1 or a scalar-field dominant solution with \Omega_\vp=1.Comment: 21 pages, 5 figures; minor clarifications added, typos corrected and references updated; final version to appear in JCA

Dark energy problem: from phantom theory to modified Gauss-Bonnet gravity

The solution of dark energy problem in the models without scalars is presented. It is shown that late-time accelerating cosmology may be generated by the ideal fluid with some implicit equation of state. The universe evolution within modified Gauss-Bonnet gravity is considered. It is demonstrated that such gravitational approach may predict the (quintessential, cosmological constant or transient phantom) acceleration of the late-time universe with natural transiton from deceleration to acceleration (or from non-phantom to phantom era in the last case).Comment: LaTeX 8 pages, prepared for the Proceedings of QFEXT'05, minor correctons, references adde