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Biomedical subjects

R Bhattacharyya

Publications and source records attributed to R Bhattacharyya.

At least 19 recordsLinked to original sources

Modeling the role of diffusion coefficients on Turing instability in a reaction-diffusion prey-predator system.

The paper is concerned with the effect of variable dispersal rates on Turing instability of a non-Lotka-Volterra reaction-diffusion system. In ecological applications, the dispersal rates of different species tends to oscillate in time. This oscillation is modeled by temporal variation in the diffusion coefficient with large as well as small periodicity. The case of large periodicity is analyzed using the theory of Floquet multipliers and that of the small periodicity by using Hill's equation. The effect of such variation on the resulting Turing space is studied. A comparative analysis of the Turing spaces with constant diffusivity and variable diffusivities is performed. Numerical simulations are carried out to support analytical findings.

Algorithms↗

Spheromak as a relaxed state with minimum dissipation.

The principle of minimum dissipation of energy is utilized to obtain the spheromak configuration as a relaxed state. The Euler-Lagrange equation for the minimum dissipative relaxed state is solved in terms of Chandrasekhar-Kendall eigenfunctions analytically generalized in the complex domain. This state is non-force-free and further shows the nonconstancy of the ratio of parallel current to the magnetic field.

Journal Article↗

A novel missense mutation in lysosomal sulfamidase is the basis of MPS III A in a spontaneous mouse mutant.

Sanfilippo syndrome type III A (Mucopolysaccharidosis (MPS) III A) is a rare, autosomal recessive, lysosomal storage disease, characterized by the accumulation of heparan sulfate and the loss of function of lysosomal heparan N-sulfatase activity. The disease leads to devastating mental and physical consequences and a mouse model that can be used to explore gene therapy and enzyme or cell replacement therapies is needed. We have previously identified a mouse with low sulfamidase activity and symptoms and pathologies typical of MPS III A (Bhaumik, M., Muller, V. J., Rozaklis, T., Johnson, L., Dobrenis, K., Bhattacharyya, R., Wurzelmann, S., Finamore, P., Hopwood, J. J., Walkley, S. U., and Stanley, P. [1999] A mouse model for mucopolysaccharidosis type III A (Sanfilippo syndrome). Glycobiology 9, 1389--1396). We now show that the sulfamidase gene of the MPS III A mouse carries a novel mutation (G91A) that gives an amino acid change (D31N) likely to interfere with the coordination of a divalent metal ion in the active site of this sulfatase. This spontaneous mouse mutant is an excellent model for MPS III A in humans as this disease often arises due to a missense mutation in lysosomal sulfamidase.

Amino Acid Sequence↗

High frequency in vitro propagation of Phyllanthus amarus Schum. & Thom. by shoot tip culture.

With the aim of micropropagation of Phyllanthus amarus, an important medicinal herb, shoot tips were cultured in Murashige and Skoog's medium supplemented with kinetin/ BAP singly or in combination with IAA. Growth regulators at lower range (0.1-1.0 mg L(-1)) stimulated direct regeneration of shoots. Kinetin was superior to BAP and kinetin-IAA combination was more suitable than kinetin alone. About 15 shoots were yielded per explant after 30 days of culture in the medium containing kinetin and IAA both at 0.1mg L(-1). The cluster of proliferated shoots elongated and rooted simultaneously under the same treatment following another subculture, thus shortening the total time schedule of micropropagation. Shoot tips of regenerated shoots were continuously used to regenerate new shoots with periodic transfer to fresh medium resulting in a steady supply of normal, healthy plants without any deviation in the production rate during a continuous one year culture. Micropropagated plants were successfully established in soil with high survivality (80%).

Botany↗

New evidence for an extra-hepatic role of N-acetylglucosaminyltransferase III in the progression of diethylnitrosamine-induced liver tumors in mice.

N-acetylglucosaminyltransferase III (GlcNAc-TIII) is encoded by the Mgat3 gene and catalyzes the addition of the bisecting GlcNAc to the core of N-glycans. Mice lacking GlcNAc-TIII due to the insertion mutation Mgat3tmlPst (termed Mgat3neo), exhibit retarded progression of liver tumors induced by diethylnitrosamine (DEN; M. Bhaumik et al, Cancer Res., 58: 2881-2887, 1998). This phenotype seemed to be due to a reduction, in activity or amount, of a circulating glycoprotein(s) that enhances DEN-induced liver tumor progression. Here, we provide new evidence to support this hypothesis. First, we show that mice with a deletion mutation of the Mgat3 gene coding exon (Mgat3tmlJxm, termed Mgat3delta) also exhibit retarded progression of DEN-induced liver tumors. At 7 months there was a significant decrease in liver weight (approximately 27%; P < 0.01), reflecting reduced tumor burden in Mgat3delta/delta mice. In addition, tumors were generally fewer and smaller, and histological changes were less severe in Mgat3delta/delta livers. Therefore, tumor progression is retarded in mice with two different null mutations in the Mgat3 gene. Second, we show that the development of DEN-induced tumors is unaltered by high levels of GlcNAc-TIII in the liver of transgenic mice. The Mgat3 gene coding exon under the control of the major urinary protein (MUP) promoter was used to generate transgenic mice that express GlcNAc-TIII in liver. Following DEN injection and phenobarbitol treatment, however, no significant differences were observed between MUP/Mgat3 transgenic and control mice in either tumor numbers or liver weight. The combined data provide strong evidence that retarded progression of tumors in mice lacking GlcNAc-TIII is due to the absence of the bisecting GlcNAc residue on N-glycans of a circulating glycoprotein(s) from a tissue other than liver.

Alleles↗

Galpha 13 requires palmitoylation for plasma membrane localization, Rho-dependent signaling, and promotion of p115-RhoGEF membrane binding.

Most heterotrimeric G protein alpha subunits are covalently modified by palmitate attached to one or more N-terminal cysteine residues. Although a wide variety of proteins undergo palmitoylation, the role of this fatty acid modification in G protein signaling is not well understood. Thus, we examined the role of palmitoylation of alpha(13), a G protein alpha subunit that regulates many pathways involved in cell growth. Both N-terminal cysteines at positions 14 and 18 were required for palmitoylation. Mutant alpha(13), in which both cysteines were changed to serines, failed to localize to plasma membranes in transfected cells and failed to activate Rho-dependent serum response factor-mediated transcription and actin stress fiber formation. However, nonpalmitoylated, cysteine to serine mutant alpha(13) retained the ability to co-immunoprecipitate with a direct effector, p115-RhoGEF. Finally, we report the novel observation that activated alpha(13) induces a redistribution of p115-RhoGEF from the cytoplasm to plasma membranes, but non-palmitoylated mutants of alpha(13) fail to cause p115-RhoGEF translocation. These findings identify palmitoylation of alpha(13) as critical for its proper membrane localization and signaling and provide insight into the mechanism of activation of Rho-dependent signaling pathways by alpha(13).

Amino Acid Sequence↗

Mapping of a palmitoylatable band 3-binding domain of human erythrocyte membrane protein 4.2.

Evidence accumulated over the years suggests that human erythrocyte membrane protein 4.2 is one of the proteins involved in strengthening the cytoskeleton-membrane interactions in the red blood cell. Deficiency of protein 4.2 is linked with a variety of hereditary haemolytic anaemia. However, the interactions of protein 4.2 with other proteins of the erythrocyte membrane remain poorly understood. The major membrane-binding site for protein 4.2 resides on the cytoplasmic domain of band 3 (CDB3). In order to carry out an initial characterization of its interaction with the CDB3, protein 4. 2 was subjected to proteolytic cleavage and gel renaturation assay, and the 23-kDa N-terminal domain was found to interact with band 3. This domain contained two putative palmitoylatable cysteine residues, of which cysteine 203 was identified as the palmitoylatable cysteine. Recombinant glutathione S-transferase-fusion peptides derived from this domain were characterized with respect to their ability to interact with the CDB3. Whereas these studies do not rule out the involvement of other subsites on protein 4.2 in interaction with the CDB3, the evidence suggests that the region encompassing amino acid residues 187-211 is one of the domains critical for the protein 4.2-CDB3 interaction. This is also the first demonstration that palmitoylation serves as a positive modulator of this interaction.

Amino Acid Sequence↗

A mouse model for mucopolysaccharidosis type III A (Sanfilippo syndrome).

Mucopolysaccharidosis type III A (MPS III A, Sanfilippo syndrome) is a rare, autosomal recessive, lysosomal storage disease characterized by accumulation of heparan sulfate secondary to defective function of the lysosomal enzyme heparan N- sulfatase (sulfamidase). Here we describe a spontaneous mouse mutant that replicates many of the features found in MPS III A in children. Brain sections revealed neurons with distended lysosomes filled with membranous and floccular materials with some having a classical zebra body morphology. Storage materials were also present in lysosomes of cells of many other tissues, and these often stained positively with periodic-acid Schiff reagent. Affected mice usually died at 7-10 months of age exhibiting a distended bladder and hepatosplenomegaly. Heparan sulfate isolated from urine and brain had nonreducing end glucosamine- N -sulfate residues that were digested with recombinant human sulfamidase. Enzyme assays of liver and brain extracts revealed a dramatic reduction in sulfamidase activity. Other lysosomal hydrolases that degrade heparan sulfate or other glycans and glycosaminoglycans were either normal, or were somewhat increased in specific activity. The MPS III A mouse provides an excellent model for evaluating pathogenic mechanisms of disease and for testing treatment strategies, including enzyme or cell replacement and gene therapy.

Animals↗

Spatial and temporal visualization of gases and vapours in air using computed tomography. Numerical studies.

Numerical studies were performed to evaluate a new method for human exposure assessment and source monitoring, based upon optical remote sensing (ORS) and computed tomography (CT). With an ORS-CT system, two-dimensional maps of chemical concentrations in air, with good spatial and temporal resolution, can be created over a confined space such as a workplace room. The ORS-CT system was evaluated using 15 simulated test maps that model the generation and dispersion of contaminant plumes over time. A program simulated field measurements from these maps assuming different remote sensing scan times. Using these measurements, reconstructed maps were generated and compared with original maps. Qualitative and quantitative methods were used to evaluate the effect on reconstruction quality of sample time, number of iterations used by the maximum likelihood expectation maximization reconstruction algorithm and sample density. For this study, scanning an entire room in 10 min was adequate for exposure evaluation, source monitoring and leak detection.

Air Pollutants↗

Development of a genus specific primer set for detection of Leishmania parasites by polymerase chain reaction.

We have compared the sequences of a major class of kinetoplast DNA (kDNA) minicircle (pLURkE3) of Leishmania strain UR6 with other minicircle sequences from different Leishmania species. Alignment of these sequences allowed the selection of a pair of oligonucleotides suitable as primers in polymerase chain reaction (PCR) which is specific for Leishmania parasites. PCR with this genus-specific primer set is capable of detecting 1 femtogram of kDNA. These primers have been tested with kDNAs from both old world and new world Leishmania species. The results indicate that the primers may be suitable for detection of any kind of leishmaniasis.

Animals↗

Development of bronchus-associated lymphoid tissue in goats.

Development of bronchus-associated lymphoid tissue (BALT) was studied in clinically healthy and diseased Assam local goats. Animals were sacrificed before term as well as at different postnatal periods to screen lung sections for the presence of BALT. In a retrospective study sections prepared from pneumonic lungs were examined for any alteration of BALT. No BALT-like structure was found in neonatal goats. Bronchial lymphoid structures appeared in half of the animals from 1 month of age onward. The frequency of the BALT/4.5 cm2 of lung section ranged from one to two in 1-month-old and three to six in 1-year-old goats. In pneumonic lungs BALT became hyperplastic, and the size was also increased. The incidence of BALT was increased in lungs with fibrotic pneumonia. The number of BALT/section was high (five to eight/4.5-cm2 area) in mesenchymal cell proliferation. The present study shows that BALT did not develop in prenatal periods. But in the presence of potent antigens lymphoid aggregates appeared in the bronchial lamina propria of normal and diseased lungs.

Animals↗

Application of polymerase chain reaction with specific and arbitrary primers to identification and differentiation of Leishmania parasites.

Two oligonucleotide primers Lsmc1 and Lsmv1 derived from the conserved and the variable region of a major class kinetoplast DNA (kDNA) minicircle (pLURkE3) of Leishmania strain UR6 were used for the polymerase chain reaction (PCR) in order to amplify a 461-bp fragment from the kDNAs of different Leishmania species. These primers amplify the specific fragment from the kDNAs of cutaneous species only. The cutaneous species can further be distinguished by randomly amplified polymorphic DNA (RAPD) analysis of the kDNAs of these organisms using arbitrarily chosen oligonucleotides. The arbitrary primers also generate polymorphic DNA fingerprints at the genomic level with different L. donovani isolates. The results indicate that the PCR and arbitrarily primed PCR (AP-PCR) may be extremely useful approaches for identifying and distinguishing Leishmania parasites.

Animals↗

L-lysine production by S-2-aminoethyl-L-cysteine-resistant mutants of Arthrobacter globiformis.

Using mutagenesis with N-methyl-N'-nitro-N-nitrosoguanidine, a number of homoserine auxotrophs have been isolated from a glutamate-producing Arthrobacter globiformis excreting L-lysine in good amounts. For further improvement, mutants resistant to the lysine analog S-(2-aminoethyl)-L-cysteine have been isolated from homoserine auxotrophs. For the three potent mutants tested, White's medium was found to be the best. Glucose, ammonium nitrate and biotin were found to be optimum at 280 mmol/L, 40 mmol/L and 22 nmol/L, respectively. With optimal glucose, ammonium nitrate and biotin, the strain AECrVI yielded 36 g lysine per L in flask culture.

Arthrobacter↗

Synthesis, characterization, and in vitro cytotoxic effects of K4 [PtCl2ATP].

An antineoplastic agent, cis-K4 [PtCl2ATP] has been synthesized and characterized, using elemental analysis, solution conductance, thermoanalysis, infrared, NMR spectroscopy, and circular dichroism studies. The in vitro cytotoxic effect imparted by this compound on Dalton's Lymphoma cells has been assessed by Trypan blue dye exclusion method and 51Cr release assays.

Adenosine Triphosphate↗

Antitumour activities of copper-ATP complex on transplantable murine lymphoma.

A synthetic metal-nucleotide complex [Cu3(ATP)26H2O]2- has been found to have a significant tumour inhibitory effect on Dalton's lymphoma. Moreover, the haematopoietic system of the treated hosts is favourably disposed and the life span is much increased. It is noteworthy that the tumour inhibitory effect is enhanced by combination therapy.

Adenosine Triphosphate↗

Recurrent perforation complicating intestinal neurofibromatosis.

A patient with diffuse intestinal neurofibromatosis who presented with recurrent small bowel perforation is described. Such recurrent perforation has not been reported previously. Management at first perforation consisted of laparotomy, and excision of the perforated nodular lesion, with removal of the gall-bladder and appendix. The diagnosis of von Recklinghausen's disease was confirmed by skin biopsy. Management of the second perforation was conservative, with administration of intravenous antibiotics, fluid replacement therapy, and nasogastric suction. The third perforation was treated surgically, with resection of the small bowel, leaving approximately 50 cm of small bowel. Such an approach represented a compromise between cure of the neurofibromatosis and leaving sufficient small bowel to allow satisfactory alimentation.

Adult↗