Department of Bioscience & Bioengineering

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Expansion of GAA repeats in the intron of the frataxin gene is involved in the autosomal recessive Friedreich's ataxia (FRDA). The GAA repeats arise from a stretch of adenine residues of an Alu element. These repeats have a size ranging from 7–38 in the normal population, and expand to thousands in the affected individuals. The mechanism of origin of GAA repeats, their polymorphism and stability are not well understood. In this study, we have carried out an extensive analysis of GAA repeats at several loci in the humans. This analysis indicates the association of a majority of GAA repeats with the 3′ end of an “A” stretch present in the Alu repeats. Further, the prevalence of GAA repeats correlates with the evolutionary age of Alu subfamilies as well as with their relative frequency in the genome. Our study on GAA repeat polymorphism at some loci in the normal population reveals that the length of the GAA repeats is determined by the relative length of the flanking A stretch. Based on these observations, a possible mechanism for origin of GAA repeats and modulatory effects of flanking sequences on repeat instability mediated by DNA triplex is proposed. © 2002 Taylor & Francis Group, LLC.

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Journal of Biomolecular Structure and Dynamics

Origin and instability of gaa repeats: Insights from alu elements

After long-standing loss of afferents from the hand, the hand representation in area 3b of the somatosensory cortex of monkeys becomes responsive to touch on the face. Because the reactivation of deprived hand cortex by the face inputs could depend on axonal connections across the hand-face border, we determined the extent of such connections in New World marmosets, owl monkeys, and squirrel monkeys. Small injections of anatomic tracers were placed in the hand or the face representations after these representations were identified by microelectrode recordings. The positions of retrogradely labeled neurons were plotted in processed brain sections cut parallel to the brain surface, and their locations were related to anatomic isomorphs of the hand and face representations revealed in adjacent brain sections stained for myelin. In these sections, the hand-face border was clearly visualized as a myelin-poor septum. The intrinsic connections of area 3b labeled by injections in either the hand or face representations were almost completely confined to their respective representation, and very few neurons projected across the border. In addition, neurons in the somatosensory thalamus labeled by injections in either face or hand representations were confined to either VPM, representing the face, or the hand subnucleus of VPL. Thus the reactivation of hand cortex by face stimulation does not depend on a previously existing network of intrinsic cortical connections across the hand-face border, or mismatched thalamocortical projections. © 2002 Wiley-Liss, Inc.

Journal of Comparative Neurology

Few intrinsic connections cross the hand-face border of area 3b of new world monkeys

Physica A: Statistical Mechanics and its Applications

Physica A - Statistical Mechanics and its Applications: Preface

Journal of Biosciences

Adult brain plasticity - What is revealed is exciting, what is hidden is critical

We report particle dynamics based studies of impulse propagation in a chain of elastic beads with dissipative contacts and with randomly distributed masses. The interaction between the beads is characterized by the potential V(δ)∼δn, δ ≥ 0 being grain overlap, n 〉 2 and at zero external loading, i.e., under conditions of "sonic vacuum" in which sound cannot propagate through the chain [J. Appl. Mech. Technol. Phys. 5 (1983) 733]. In the earlier work, we have confirmed the studies of Nesterenko and coworkers and have reported that impulses propagate as solitary waves in the system of interest in the absence of dissipation and disorder [Physica A 268 (1999) 644]. In the present study, we first discuss the effects of restitution and velocity dependent friction on the propagation of the impulse. We next report that the maximum energy Emax of the solitary wave as it propagates from a chain of monodisperse grains of mass m to a chain with masses m(1 +r(z)ε), where -1≤r(z)≤1 and ε=const. that measures the degree of randomness, decays with linear distance traveled z as exp(-αEz), αE∼ ε2+f(n), f(n) being some n dependent constant for 2 〈 n 〈 ∞. In monodisperse chains, the velocity of the solitary wave c∼Emax(n-2)/2n. In polydisperse chains, we show that the propagation speed of a non-dispersive solitary wave decays with distance as exp(-αcz), where αc = αE(n-2)/2n. © 2001 Elsevier Science B.V. All rights reserved.

Physica D: Nonlinear Phenomena

Impulse propagation in dissipative and disordered chains with power-law repulsive potentials

The canonical ensemble relaxation function of a particle in a symmetric anharmonic potential well in D = 1 is known to exhibit slow algebraic behavior [S. Sen, R. S. Sinkovits and S. Chakravarti, Phys. Rev. Lett. 77, 4855 (1996); R. S. Sinkovits, S. Sen, J. C. Phillips, and S. Chakravarti, Phys. Rev. E 59, 6497 (1999)]. In the present work, we report a study of relaxation of a particle in symmetric and asymmetric quartic anharmonic potential wells of the form V(x,y) = 1/2 (x2 + Cy2) + 1/4 (x2 + Cy2)2 in D = 2. The relaxation in the above system is identical to that in D = 1 wells when C = 0 (since it is then a D = 1 system) and C = 1. However, for O &lt; C &lt; 1 and for C≫1, the frequencies associated with well dynamics are strongly affected and hence the power spectra are altered as a function of C Our calculations suggest that the exponents of the long-time tails associated with the relaxation processes are insensitive to D. In closing, we comment on the consequences of our analysis for the study of slow dynamics in interacting many-particle systems that are connected by harmonic springs with the individual particles in anharmonic potential wells. ©2001 The American Physical Society.

Physical Review E - Statistical, Nonlinear, and Soft Matter Physics

Relaxation of classical particles in two-dimensional anharmonic single-well potentials

The equation of motion for a bead in a chain of uncompressed elastic beads in contact that interact via the potential [Formula Presented] δ being overlap, supports solitary waves and does not accommodate sound propagation [V. Nesterenko, J. Appl. Mech. Tech. Phys. 5, 733 (1983)]. We present an iteratively exact solution to describe the solitary wave as a function of material parameters and a universal, infinite set of coefficients, which depend only on n. We compute any arbitrary number of coefficients to desired accuracy and show that only the first few coefficients of our solution significantly improves upon Nesterenko’s solution. The improved solution is a necessary step to develop a theoretical understanding of the formation of secondary solitary waves [M. Manciu, et al., Phys. Rev. E 63, 011614 (2001)]. © 2001 The American Physical Society.

Physical Review E - Statistical Physics, Plasmas, Fluids, and Related Interdisciplinary Topics

Solitary wave dynamics in generalized Hertz chains: An improved solution of the equation of motion

The canonical ensemble relaxation function of a particle in a symmetric anharmonic potential well in D = 1 is known to exhibit slow algebraic behavior [S. Sen, R. S. Sinkovits and S. Chakravarti, Phys. Rev. Lett. 77, 4855 (1996); R. S. Sinkovits, S. Sen, J. C. Phillips, and S. ChakravartiPhys. Rev. E 59, 6497 (1999)]. In the present work, we report a study of relaxation of a particle in symmetric and asymmetric quartic anharmonic potential wells of the form V(x,y)= 1/2(x2 + Cy2)+ 1/4 (x2+ Cy2)2 in D = 2. The relaxation in the above system is identical to that in D= 1 wells when C=0 (since it is then a D= 1 system) and C= 1. However, for 0 &lt;C&lt;1 and for C≫1, the frequencies associated with well dynamics are strongly affected and hence the power spectra are altered as a function of C. Our calculations suggest that the exponents of the long-time tails associated with the relaxation processes are insensitive to D. In closing, we comment on the consequences of our analysis for the study of slow dynamics in interacting many-particle systems that are connected by harmonic springs with the individual particles in anharmonic potential wells. ©2001 The American Physical Society.

Spinocerebellar ataxia 2 (SCA2) is an autosomal dominant neurodegenerative disorder that results from the expansion of a cryptic CAG repeat within the exon 1 of the SCA2 gene. The CAG repeat in normal individuals varies in length from 14 to 31 repeats and is frequently interrupted by one or more CAA triplets, whereas the expanded alleles contain a pure uninterrupted stretch of 34 to 59 CAG repeats. We have previously reported the presence of a limited pool of 'ancestral' or 'at risk' haplotypes for the expanded SCA2 alleles in the Indian population. We now report the identification of two novel single nucleotide polymorphisms (SNPs) in exon 1 of the SCA2 gene and their characterization in 215 normal and 64 expanded chromosomes. The two biallelic SNPs distinguished two haplotypes, GT and CC, each of which formed a predominant haplotype associated with normal and expanded SCA2 alleles. All the expanded alleles segregated with CC haplotype, which otherwise was associated with only 29.3% of the normal chromosomes. CAA interspersion analysis revealed that majority of the normal alleles with CC haplotype were either pure or lacked the most proximal 5′ CAA interruption. The repeat length variation at SCA2 locus also appeared to be polar with changes occurring mostly at the 5′ end of the repeat. Our results demonstrate that CAA interruptions play an important role in conferring stability to SCA2 repeat and their absence predisposes alleles towards instability and pathological expansion. Our study also provides new haplotypes associated with SCA2 that should prove useful in further understanding the mutational history and mechanism of repeat instability at the SCA2 locus.

Fulltext

Human Molecular Genetics

CAG repeat instability at SCA2 locus: Anchoring CAA interruptions and linked single nucleotide polymorphisms

The canonical ensemble relaxation function of a particle in a symmetric anharmonic potential well in [formula presented] is known to exhibit slow algebraic behavior [S. Sen, R. S. Sinkovits and S. Chakravarti, Phys. Rev. Lett. 77, 4855 (1996); R. S. Sinkovits, S. Sen, J. C. Phillips, and S. Chakravarti, Phys. Rev. E 59, 6497 (1999)]. In the present work, we report a study of relaxation of a particle in symmetric and asymmetric quartic anharmonic potential wells of the form [formula presented] in [formula presented] The relaxation in the above system is identical to that in [formula presented] wells when [formula presented] (since it is then a [formula presented] system) and [formula presented] However, for [formula presented] and for [formula presented] the frequencies associated with well dynamics are strongly affected and hence the power spectra are altered as a function of C. Our calculations suggest that the exponents of the long-time tails associated with the relaxation processes are insensitive to D. In closing, we comment on the consequences of our analysis for the study of slow dynamics in interacting many-particle systems that are connected by harmonic springs with the individual particles in anharmonic potential wells. © 2001 The American Physical Society.