PubMed Health⌕ Search

Biomedical subjects

C Dasgupta

Publications and source records attributed to C Dasgupta.

At least 19 recordsLinked to original sources
PubMed2002

Stochastic neural network model for spontaneous bursting in hippocampal slices.

A biologically plausible, stochastic, neural network model that exhibits spontaneous transitions between a low-activity (normal) state and a high-activity (epileptic) state is studied by computer simulation. Brief excursions of the network to the high-activity state lead to spontaneous population bursting similar to the behavior observed in hippocampal slices bathed in a high-potassium medium. Although the variability of interburst intervals in this model is due to stochasticity, first return maps of successive interburst intervals show trajectories that resemble the behavior expected near unstable periodic orbits (UPOs) of systems exhibiting deterministic chaos. Simulations of the effects of the application of chaos control, periodic pacing, and anticontrol to the network model yield results that are qualitatively similar to those obtained in experiments on hippocampal slices. Estimation of the statistical significance of UPOs through surrogate data analysis also leads to results that resemble those of similar analysis of data obtained from slice experiments and human epileptic activity. These results suggest that spontaneous population bursting in hippocampal slices may be a manifestation of stochastic bistable dynamics, rather than of deterministic chaos. Our results also question the reliability of some of the recently proposed, UPO-based, statistical methods for detecting determinism and chaos in experimental time-series data.

Action Potentials↗
PubMed2002

Experimental persistence probability for fluctuating steps.

The persistence behavior for fluctuating steps on the Si(111)-(sqrt[3]xsqrt[3])R30 degrees -Al surface was determined by analyzing time-dependent STM images for temperatures between 770 and 970 K. Using the standard persistence definition, the measured persistence probability displays power-law decay with an exponent of theta=0.77+/-0.03. This is consistent with the value of theta=3/4 predicted for attachment-detachment limited step kinetics. If the persistence analysis is carried out in terms of return to a fixed-reference position, the measured probability decays exponentially. Numerical studies of the Langevin equation used to model step motion corroborate the experimental observations.

Journal Article↗
PubMed2002

Neural network model for apparent deterministic chaos in spontaneously bursting hippocampal slices.

A neural network model that exhibits stochastic population bursting is studied by simulation. First return maps of interburst intervals exhibit recurrent unstable-periodic-orbit(UPO)-like trajectories similar to those found in experiments on hippocampal slices. Applications of various control methods and surrogate analysis for UPO detection also yield results similar to those of experiments. Our results question the interpretation of the experimental data as evidence for deterministic chaos and suggest caution in the use of UPO-based methods for detecting determinism in time-series data.

Hippocampus↗
PubMed2001

Vortex lattice melting in layered superconductors with periodic columnar pins.

The melting of the vortex lattice in highly anisotropic, layered superconductors with commensurate, periodic columnar pins is studied in a geometry where magnetic field and columnar pins are normal to the layers. Thermodynamic properties and equilibrium density distributions are obtained from numerical minimization of an appropriate free-energy functional. We find a line of first-order transitions that ends at a critical point as the pin concentration is increased. We quantitatively determine the location of this critical point and show that it is experimentally accessible.

Journal Article↗
PubMed2001

Identification of connexin43 (alpha1) gap junction gene mutations in patients with hypoplastic left heart syndrome by denaturing gradient gel electrophoresis (DGGE).

Gap junction channels formed by the connexin43 protein are considered to play crucial roles in development and function because they allow the direct cell-to-cell exchange of molecules that mediate multiple signaling events. Previous results have shown that connexin43 channels are intricately gated by phosphorylation and that disruption of this regulation gives rise to severe heart malformations and defects of laterality in human, chick and frog. Here we report the identification of connexin43 gene mutations that represent a minor population of connexin43 alleles, which could be reliably detected by using denaturing gradient gel electrophoresis (DGGE) to visualize normal and mutant DNAs that were separately sequenced. In contrast, sequencing of total PCR products without DGGE-pre-selection failed to consistently identify these mutations. Forty-six controls and 20 heart transplant recipients were examined in this study. In the latter group, 14 children had hypoplastic left heart syndrome (HLHS) in which connexin43 gene defects were detected in eight. The remaining six transplant patients with HLHS and all controls showed no defects. All eight HLHS children with gene defects had the same four substitutions: two that were silent polymorphisms, and two that were missense, replacing arginine codons at positions 362 and 376 with codons for glutamines. All four of these substitutions are identical to the nucleotide sequence of the connexin43 pseudogene, suggesting the possibility of an illicit recombination. A breakpoint region was identified 5' to the mutation site in a 63bp domain that is 100% identical in the gene and pseudogene. Results from in vitro phosphorylation indicate that the absence of arginines 362 and 376 completely abolishes phosphorylation in the connexin43 channel regulation domain suggesting a possible mechanism for the pathologies associated with HLHS.

Base Sequence↗
PubMed2000

Equilibrium and dynamical properties of the axial next-nearest-neighbor ising chain at the multiphase point

We study the equilibrium and dynamical properties of the axial next-nearest-neighbor Ising chain at the multiphase point. An interesting property of the system is the macroscopic degeneracy of the ground state leading to finite zero-temperature entropy. In our equilibrium study we consider the effect of softening the spins. We show that the degeneracy of the ground state is lifted and there is a qualitative change in the low-temperature behavior of the system with a well-defined low-temperature peak of the specific heat that carries the thermodynamic "weight" of the ground state entropy. In our study of the dynamical properties, the stochastic Kawasaki dynamics is considered. The Fokker-Planck operator for the process corresponds to a quantum spin Hamiltonian similar to the Heisenberg ferromagnet but with constraints on allowed states. This leads to a number of differences in its properties, which are obtained through exact numerical diagonalization, simulations, and by obtaining various analytic bounds.

Journal Article↗
PubMed2000

Phase diagram of a hard-sphere system in a quenched random potential: A numerical study

We report numerical results for the phase diagram in the density-disorder plane of a hard-sphere system in the presence of quenched, random, pinning disorder. Local minima of a discretized version of the Ramakrishnan-Yussouff free energy functional are located numerically and their relative stability is studied as a function of the density and the strength of disorder. Regions in the phase diagram corresponding to liquid, glassy, and nearly crystalline states are mapped out, and the nature of the transitions is determined. The liquid to glass transition changes from first to second order as the strength of the disorder is increased. For weak disorder, the system undergoes a first-order crystallization transition as the density is increased. Beyond a critical value of the disorder strength, this transition is replaced by a continuous glass transition. Our numerical results are compared with those of analytical work on the same system. Implications of our results for the field-temperature phase diagram of type-II superconductors are discussed.

Journal Article↗
PubMed2000

Retrieval properties of a Hopfield model with random asymmetric interactions.

The process of pattern retrieval in a Hopfield model in which a random antisymmetric component is added to the otherwise symmetric synaptic matrix is studied by computer simulations. The introduction of the anti-symmetric component is found to increase the fraction of random inputs that converge to the memory states. However, the size of the basin of attraction of a memory state does not show any significant change when asymmetry is introduced in the synaptic matrix. We show that this is due to the fact that the spurious fixed points, which are destabilized by the introduction of asymmetry, have very small basins of attraction. The convergence time to spurious fixed-point attractors increases faster than that for the memory states as the asymmetry parameter is increased. The possibility of convergence to spurious fixed points is greatly reduced if a suitable upper limit is set for the convergence time. This prescription works better if the synaptic matrix has an antisymmetric component.

Algorithms↗
PubMed1999

Misregulation of connexin43 gap junction channels and congenital heart defects.

Although there is general agreement that gap junction channels formed by the connexin43 (Cx43; alpha 1) protein most likely have important roles during heart development, evidence to support this view has been equivocal. Lacking this information, it is difficult to understand the basis of heart malformations found in the Cx43 knockout mice and in children with a severe form of visceroatrial heterotaxia that coincides with missense mutations of the Cx43 gene. To address this issue we used a combination of western blots to follow the emergence of Cx43 in heart, and in vitro and in vivo phosphorylation to assess the effect of mutation on Cx43 phosphorylation. We evaluated the activity ratios of cAMP-dependent protein kinase and protein kinase C in hearts of 8.5-day-old mouse embryos through to birth. The results demonstrate that Cx43 is present in the native phosphorylated species in day 8.5 hearts and thereafter. Further, the activities of cAMP-dependent protein kinase and protein kinase C are mirror images of each other during the 8.5-10.5 days of early heart development. From these results we conclude that Cx43 gap junction channels are present and capable of being regulated by day 8.5 of embryonic heart development.

Amino Acid Sequence↗
PubMed1998

Melanin content and downregulation of glutathione S-transferase contribute to the action of L-buthionine-S-sulfoximine on human melanoma.

L-buthionine-S,R-sulfoximine (L-S,R-BSO) was enriched for the active L-buthionine-S-sulfoximine (L-S-BSO) diastereomer. Comparative analysis was performed to determine if this enriched form possessed an increased capacity to deplete glutathione (GSH), and to inhibit the proliferation of tumor cell lines and fresh human tumor samples. Increased activity was observed for the enriched preparation of L-S-BSO in direct proportion to its increased L-S-diastereomeric percentage. Significant antitumor activity towards melanoma, breast and ovarian carcinoma specimens was noted, with the greatest activity directed against malignant melanoma. The activity of BSO on melanoma specimens was found to be correlated with their melanin content, suggesting that free radicals generated during melanin synthesis may become cytotoxic after GSH-dependent scavenging has been eliminated by BSO treatment. The antimelanoma activity of melphalan and BCNU were found to be significantly enhanced in combination with L-S-BSO. With respect to the mechanism of L-S-BSO synergy with alkylators, L-S-BSO treatment of M14 and ZAZ human melanoma cell lines resulted in decreased GSH levels and glutathione S-transferase (GST) activity. Western and Northern blot analyses indicated that GST-mu was the predominant isozyme downregulated after L-S-BSO treatment. Both M14 and ZAZ cell lines selected for resistance to L-S-BSO also showed decreased levels of GST-mu expression. However, in drug free media GST enzyme activity returned to pre-treatment levels without altering the BSO-resistance status of the cell lines. We conclude that L-S-BSO may be an active agent in the treatment of melanoma, and that it may enhance alkylator activity on melanoma through depletion of GSH and down-regulation of GST expression. Purified L-S-BSO should be explored clinically as an active agent for the treatment of melanoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Selective and synergistic activity of L-S,R-buthionine sulfoximine on malignant melanoma is accompanied by decreased expression of glutathione-S-transferase.

L-buthionine-S,R-sulfoximine (BSO) selectivley inhibits glutathione (GSH) synthesis. Malignant melanoma may be uniquely dependent on GSH and its linked enzymes, glutathione S-transferase (GST) and GSH-peroxidase, for metabolism of reactive orthoquinones and peroxides produced during melanin synthesis. We compared the in vitro effects of BSO on melanoma cell lines and fresh melanoma specimens (n = 118) with breast and ovarian cell lines and solid tumors (n = 244). IC50 values (microM) for BSO on melanoma, breast and ovarian tumor specimens were 1.9, 8.6, and 29, respectively. The IC90 for melanoma was 25.5 microM, a level 20-fold lower than steady state levels achieved clinically. The sensitivity of individual specimens of melanoma correlated with their melanin content (r = 0.63). BSO synergistically enhanced BCNU activity against melanoma cell lines and human tumors. We followed GSH levels, GST enzyme activity, GST isoenzyme profiles and mRNA levels after BSO. BSO (50 microM) treatment for 48 hr resulted in a 95% decrease in ZAZ and M14 melanoma cell line GSH levels, and a 60% decrease in GST enzyme activity. GST-mu protein and mRNA levels were significantly reduced in both cell lines. GST-pi expression was unaffected. These data suggest that BSO action on melanoma may be related to GSH depletion, diminishing the capacity to scavenge toxic metabolites produced during melanin synthesis. We report here for the first time that BSO enhancement of alkylator action may be related in part to down regulation of GST. BSO may be a clinically useful adjunct in the treatment of malignant melanoma.

Antimetabolites, Antineoplastic↗
PubMed1996

Reactivation of denatured proteins by 23S ribosomal RNA: role of domain V.

Escherichia coli ribosome, its 50S subunit, or simply the 23S rRNA can reactivate denatured proteins in vitro. Here we show that protein synthesis inhibitors chloramphenicol and erythromycin, which bind to domain V of 23S rRNA of E. coli, can inhibit reactivation of denatured pig muscle lactate dehydrogenase and fungal glucose-6-phosphate dehydrogenase by 23S rRNA completely. Oligodeoxynucleotides complementary to two regions within domain V (which cover sites of chloramphenicol resistant mutations and the putative A site of the incoming aminoacyl tRNA), but not to a region outside of domain V, also can inhibit the activity. Domain V of 23S rRNA, therefore, appears to play a crucial role in reactivation of denatured proteins.

Animals↗
PubMed1996

In vitro protein folding by ribosomes from Escherichia coli, wheat germ and rat liver: the role of the 50S particle and its 23S rRNA.

Ribosomes from a number of prokaryotic and eukaryotic sources (e.g. Escherichia coli, wheat germ and rat liver) can refold a number of enzymes which are denatured with guanidine/HC1 prior to incubation with ribosomes. In this report, we present our observations on the refolding of denatured lactate dehydrogenase from rabbit muscle and glucose-6-phosphate dehydrogenase from baker's yeast by ribosomes from E. coli, wheat germ and rat liver. The protein-folding activity of E. coli ribosomes was found to be present in 50S particles and in 23S rRNA. The 30S particle or 16S rRNA did not show any protein-folding activity. The protein-folding activity of 23S rRNA may depend on its tertiary conformation. Loss of tertiary structure, by incubation with low concentrations of EDTA, inhibited the protein-folding activity of 23S rRNA. This low concentration of EDTA had no effect on folding of the denatured enzymes by themselves.

Animals↗