Modulation of polyamines to elucidate function within osteogenesis of mesenchymal stromal cells

Snyder-Robinson Syndrome (SRS), an X-linked intellectual disability that arises in children, exhibits debilitating phenotypes like severe osteoporosis. These patients demonstrate an inability to produce mineralized new bone in comparison to the rate at which bone is resorbed, thus leading to weaker skeletal structure and atraumatic fractures. The known cause of SRS is due to loss-of-function mutations within the gene that encodes Spermine Synthase (SMS). Loss of SMS enzymatic activity, which catalyzes the conversion of polyamines spermidine into spermine, demonstrates an increase in the spermidine/spermine ratio in all documented cases of this disorder. The involvement of polyamines in osteogenesis is still not well understood, but it is apparent that maintaining strict regulation of these organic compounds is necessary for bone mineralization. Due to deficient therapeutic intervention, it is imperative to continue researching the molecular mechanisms by which the polyamine pathway regulates bone mineralization. Here we investigated the effects of exogenous supplementation of either putrescine, spermidine, or spermine throughout osteogenic differentiation within healthy human bone-marrow derived mesenchymal stromal cells (MSCs). Through this, we confirmed the ability to transport polyamines within MSCs, as well as observed inhibitory effects throughout osteogenesis. We found that excess spermidine inhibits alkaline phosphatase activity, an important osteogenic marker, while excess spermine decreases hydroxyapatite synthesis as confirmed through Alizarin red S staining. Furthermore, we observed the gene that encodes spermidine/spermine N1-acetyltransferase 1 (SAT1) depicts a powerful upregulation in expression at the mRNA level during osteogenic differentiation in healthy MSCs. To further explore this, we silenced SAT1 expression using lentiviral vectors expressing a SAT1-specific shRNA. Our preliminary studies suggest that suppressing SAT1 expression has minimal effect on osteogenesis. These data suggest that the conversion of higher polyamines into more easily excretable lower polyamines is necessary in bone development, and altogether, our studies propose that SRS is due to the accumulating spermidine interactions within cells throughout osteogenesis

Ecological theatre and the evolutionary game: how environmental and demographic factors determine payoffs in evolutionary games

In the standard approach to evolutionary games and replicator dynamics, differences in fitness can be interpreted as an excess from the mean Malthusian growth rate in the population. In the underlying reasoning, related to an analysis of "costs" and "benefits", there is a silent assumption that fitness can be described in some type of units. However, in most cases these units of measure are not explicitly specified. Then the question arises: are these theories testable? How can we measure "benefit" or "cost"? A natural language, useful for describing and justifying comparisons of strategic "cost" versus "benefits", is the terminology of demography, because the basic events that shape the outcome of natural selection are births and deaths. In this paper, we present the consequences of an explicit analysis of births and deaths in an evolutionary game theoretic framework. We will investigate different types of mortality pressures, their combinations and the possibility of trade-offs between mortality and fertility. We will show that within this new approach it is possible to model how strictly ecological factors such as density dependence and additive background fitness, which seem neutral in classical theory, can affect the outcomes of the game. We consider the example of the Hawk-Dove game, and show that when reformulated in terms of our new approach new details and new biological predictions are produced

The measurement of residual feed intake to determine feed efficiency of pregnant Hereford heifers

Abstract only availableThe large potential improvement in profitability is what makes feed efficiency such a studied and concerned topic in the beef industry today. Currently, no herd exists in the United States that has been selected solely for the purpose of measuring and improving feed efficiency. The objective of this study was to rank forty-two pregnant Hereford heifers based on their feed efficiencies, so that they may be mated to bulls of known efficiency. The long term goal of this project is to create both efficient and inefficient herds for future feed efficiency research. These heifers were acquired from various beef producers across the state to ensure genetic variation within the herd. The heifers were fed an alfalfa/grass hay to which they had ad libitum access. Their diet was 86% dry matter and contained 58% neutral detergent fiber, 38% acid detergent fiber, and 14% crude protein on a dry matter basis. The individual intake of each heifer was recorded by the GrowSafe® feed intake system. Expected feed intake was calculated as a regression of actual intake on average daily gain and metabolic mid-weight. Expected feed intake was subtracted from actual feed intake to calculate the residual feed intake value of each individual heifer. Residual feed intake was then used as a measure of feed efficiency. The average body weight at the start of the study was 488 kg. Heifers consumed on average 17.77 ± 5.24 kg/d, and the herd gained at a rate of 0.77 ± 0.32 kg/d. The most efficient heifer consumed 9.78 kg/d less than was expected, while the most inefficient heifer consumed 11.54 kg/d more than was expected. Calculating residual feed intake as a means of determining feed efficiency will enable us to establish both efficient and inefficient herds for further research.F.B. Miller Undergraduate Research Program in Animal Science

Persistent global power fluctuations near a dynamic transition in electroconvection

This is a study of the global fluctuations in power dissipation and light transmission through a liquid crystal just above the onset of electroconvection. The source of the fluctuations is found to be the creation and annihilation of defects. They are spatially uncorrelated and yet temporally correlated. The temporal correlation is seen to persist for extremely long times. There seems to be an especially close relation between defect creation/annihilat ion in electroconvection and thermal plumes in Rayleigh-B\'enard convection

Promote cooperation by localised small-world communication

The emergence and maintenance of cooperation within sizable groups of unrelated humans offer many challenges for our understanding. We propose that the humans' capacity of communication, such as how many and how far away the fellows can build up mutual communications, may affect the evolution of cooperation. We study this issue by means of the public goods game (PGG) with a two-layered network of contacts. Players obtain payoffs from five-person public goods interactions on a square lattice (the interaction layer). Also, they update strategies after communicating with neighbours in learning layer, where two players build up mutual communication with a power law probability depending on their spatial distance. Our simulation results indicate that the evolution of cooperation is indeed sensitive to how players choose others to communicate with, including the amount as well as the locations. The tendency of localised communication is proved to be a new mechanism to promote cooperation.Comment: 6 pages, 4 figure

Hysteresis at low Reynolds number: the onset of 2D vortex shedding

Hysteresis has been observed in a study of the transition between laminar flow and vortex shedding in a quasi-two dimensional system. The system is a vertical, rapidly flowing soap film which is penetrated by a rod oriented perpendicular to the film plane. Our experiments show that the transition from laminar flow to a periodic K\'arm\'an vortex street can be hysteretic, i.e. vortices can survive at velocities lower than the velocity needed to generate them.Comment: RevTeX file 4 pages + 5 (encapsulated postscript) figures. to appear in Phys.Rev.E, Rapid Communicatio

Turbulence in a free surface

We report an experimental and numerical study of turbulent fluid motion in a free surface. The flow is realized experimentally on the surface of a tank filled with water stirred by a vertically oscillating grid positioned well below the surface. Particles floating on the surface are used to visualize the flow. The effect of surface waves appears to be negligible. The flow is unconventional in that it is confined to two dimensions but does not have squared vorticity as a conservation law, that it is not divergence free and that it inherits scaling features of the mean square velocity differences S_2(R) and the vorticity fluctuations Omega(R) from the bulk 3-d turbulence.Comment: 4 pages, 4 Postscript figure

Is it possible to experimentally verify the fluctuation relation? A review of theoretical motivations and numerical evidence

The theoretical motivations to perform experimental tests of the stationary state fluctuation relation are reviewed. The difficulties involved in such tests, evidenced by numerical simulations, are also discussed.Comment: 36 pages, 4 figures. Extended version of a presentation to the discussion "Is it possible to experimentally verify the fluctuation theorem?", IHP, Paris, December 1, 2006. Comments are very welcom

Quantum-like Representation of Extensive Form Games: Wine Testing Game

We consider an application of the mathematical formalism of quantum mechanics (QM) outside physics, namely, to game theory. We present a simple game between macroscopic players, say Alice and Bob (or in a more complex form - Alice, Bob and Cecilia), which can be represented in the quantum-like (QL) way -- by using a complex probability amplitude (game's ``wave function'') and noncommutative operators. The crucial point is that games under consideration are so called extensive form games. Here the order of actions of players is important, such a game can be represented by the tree of actions. The QL probabilistic behavior of players is a consequence of incomplete information which is available to e.g. Bob about the previous action of Alice. In general one could not construct a classical probability space underlying a QL-game. This can happen even in a QL-game with two players. In a QL-game with three players Bell's inequality can be violated. The most natural probabilistic description is given by so called contextual probability theory completed by the frequency definition of probability