Hsp-90 and the biology of nematodes

BACKGROUND: Hsp-90 from the free-living nematode Caenorhabditis elegans is unique in that it fails to bind to the specific Hsp-90 inhibitor, geldanamycin (GA). Here we surveyed 24 different free-living or parasitic nematodes with the aim of determining whether C. elegans Hsp-90 was the exception or the norm amongst the nematodes. We combined these data with codon evolution models in an attempt to identify whether hsp-90 from GA-binding and non-binding species has evolved under different evolutionary constraints.<BR/>RESULTS: We show that GA-binding is associated with life history: free-living nematodes and those parasitic species with free-living larval stages failed to bind GA. In contrast, obligate parasites and those worms in which the free-living stage in the environment is enclosed within a resistant egg, possess a GA-binding Hsp-90. We analysed Hsp-90 sequences from fifteen nematode species to determine whether nematode hsp-90s have undergone adaptive evolution that influences GA-binding. Our data provide evidence of rapid diversifying selection in the evolution of the hsp-90 gene along three separate lineages, and identified a number of residues showing significant evidence of adaptive evolution. However, we were unable to prove that the selection observed is correlated with the ability to bind geldanamycin or not.<BR/>CONCLUSION: Hsp-90 is a multi-functional protein and the rapid evolution of the hsp-90 gene presumably correlates with other key cellular functions. Factors other than primary amino acid sequence may influence the ability of Hsp-90 to bind to geldanamycin

Calculations of Neutron Reflectivity in the eV Energy Range from Mirrors made of Heavy Nuclei with Neutron-Nucleus Resonances

We evaluate the reflectivity of neutron mirrors composed of certain heavy nuclei which possess strong neutron-nucleus resonances in the eV energy range. We show that the reflectivity of such a mirror for some nuclei can in principle be high enough near energies corresponding to compound neutron-nucleus resonances to be of interest for certain scientific applications in non-destructive evaluation of subsurface material composition and in the theory of neutron optics beyond the kinematic limit.Comment: 18 pages, 5 figures, 1 tabl

Cutting and Shuffling a Line Segment: Mixing by Interval Exchange Transformations

We present a computational study of finite-time mixing of a line segment by cutting and shuffling. A family of one-dimensional interval exchange transformations is constructed as a model system in which to study these types of mixing processes. Illustrative examples of the mixing behaviors, including pathological cases that violate the assumptions of the known governing theorems and lead to poor mixing, are shown. Since the mathematical theory applies as the number of iterations of the map goes to infinity, we introduce practical measures of mixing (the percent unmixed and the number of intermaterial interfaces) that can be computed over given (finite) numbers of iterations. We find that good mixing can be achieved after a finite number of iterations of a one-dimensional cutting and shuffling map, even though such a map cannot be considered chaotic in the usual sense and/or it may not fulfill the conditions of the ergodic theorems for interval exchange transformations. Specifically, good shuffling can occur with only six or seven intervals of roughly the same length, as long as the rearrangement order is an irreducible permutation. This study has implications for a number of mixing processes in which discontinuities arise either by construction or due to the underlying physics.Comment: 21 pages, 10 figures, ws-ijbc class; accepted for publication in International Journal of Bifurcation and Chao

Discrete Dynamical Systems Embedded in Cantor Sets

While the notion of chaos is well established for dynamical systems on manifolds, it is not so for dynamical systems over discrete spaces with $N$ variables, as binary neural networks and cellular automata. The main difficulty is the choice of a suitable topology to study the limit $N\to\infty$. By embedding the discrete phase space into a Cantor set we provided a natural setting to define topological entropy and Lyapunov exponents through the concept of error-profile. We made explicit calculations both numerical and analytic for well known discrete dynamical models.Comment: 36 pages, 13 figures: minor text amendments in places, time running top to bottom in figures, to appear in J. Math. Phy

Nambu-Hamiltonian flows associated with discrete maps

For a differentiable map $(x_1,x_2,..., x_n)\to (X_1,X_2,..., X_n)$ that has an inverse, we show that there exists a Nambu-Hamiltonian flow in which one of the initial value, say $x_n$, of the map plays the role of time variable while the others remain fixed. We present various examples which exhibit the map-flow correspondence.Comment: 19 page

A repurposing strategy for Hsp90 inhibitors demonstrates their potency against filarial nematodes

Novel drugs are required for the elimination of infections caused by filarial worms, as most commonly used drugs largely target the microfilariae or first stage larvae of these infections. Previous studies, conducted in vitro, have shown that inhibition of Hsp90 kills adult Brugia pahangi. As numerous small molecule inhibitors of Hsp90 have been developed for use in cancer chemotherapy, we tested the activity of several novel Hsp90 inhibitors in a fluorescence polarization assay and against microfilariae and adult worms of Brugia in vitro. The results from all three assays correlated reasonably well and one particular compound, NVP-AUY922, was shown to be particularly active, inhibiting Mf output from female worms at concentrations as low as 5.0 nanomolar after 6 days exposure to drug. NVP-AUY922 was also active on adult worms after a short 24 h exposure to drug. Based on these in vitro data, NVP-AUY922 was tested in vivo in a mouse model and was shown to significantly reduce the recovery of both adult worms and microfilariae. These studies provide proof of principle that the repurposing of currently available Hsp90 inhibitors may have potential for the development of novel agents with macrofilaricidal properties

Renormalization Group Functional Equations

Functional conjugation methods are used to analyze the global structure of various renormalization group trajectories, and to gain insight into the interplay between continuous and discrete rescaling. With minimal assumptions, the methods produce continuous flows from step-scaling {\sigma} functions, and lead to exact functional relations for the local flow {\beta} functions, whose solutions may have novel, exotic features, including multiple branches. As a result, fixed points of {\sigma} are sometimes not true fixed points under continuous changes in scale, and zeroes of {\beta} do not necessarily signal fixed points of the flow, but instead may only indicate turning points of the trajectories.Comment: A physical model with a limit cycle added as section IV, along with reference

Extension of Lorenz Unpredictability

It is found that Lorenz systems can be unidirectionally coupled such that the chaos expands from the drive system. This is true if the response system is not chaotic, but admits a global attractor, an equilibrium or a cycle. The extension of sensitivity and period-doubling cascade are theoretically proved, and the appearance of cyclic chaos as well as intermittency in interconnected Lorenz systems are demonstrated. A possible connection of our results with the global weather unpredictability is provided.Comment: 32 pages, 13 figure

A dimension-breaking phenomenon for water waves with weak surface tension

It is well known that the water-wave problem with weak surface tension has small-amplitude line solitary-wave solutions which to leading order are described by the nonlinear Schr\"odinger equation. The present paper contains an existence theory for three-dimensional periodically modulated solitary-wave solutions which have a solitary-wave profile in the direction of propagation and are periodic in the transverse direction; they emanate from the line solitary waves in a dimension-breaking bifurcation. In addition, it is shown that the line solitary waves are linearly unstable to long-wavelength transverse perturbations. The key to these results is a formulation of the water wave problem as an evolutionary system in which the transverse horizontal variable plays the role of time, a careful study of the purely imaginary spectrum of the operator obtained by linearising the evolutionary system at a line solitary wave, and an application of an infinite-dimensional version of the classical Lyapunov centre theorem.Comment: The final publication is available at Springer via http://dx.doi.org/10.1007/s00205-015-0941-