Biomedical subjects

Biswajit Das

Publications and source records attributed to Biswajit Das.

8 recordsLinked to original sources

PubMed2006

Pairing morphology with gene expression in thyroid hormone-induced intestinal remodeling and identification of a core set of TH-induced genes across tadpole tissues.

Thyroid hormone (T3) plays a central role in vertebrate post-embryonic development, and amphibian metamorphosis provides a unique opportunity to examine T3-dependent developmental changes. To establish a molecular framework for understanding T3-induced morphological change, we identified a set of gene expression profiles controlled by T3 in the intestine via microarray analysis. Samples were obtained from premetamorphic Xenopus laevis tadpole intestines after 0, 1, 3, and 6 days of T3 treatment, which induces successive cell death and proliferation essential for intestinal remodeling. Using a set of 21,807 60-mer oligonucleotide probes representing >98% of the Unigene clusters, we found that 1997 genes were differentially regulated by 1.5-fold or more during this remodeling process and were clustered into four temporal expression profiles; transiently up- or downregulated and late up- or downregulated. Gene Ontology categories most significantly associated with these clusters were proteolysis, cell cycle, development and transcription, and electron transport and metabolism, respectively. These categories are common with those found for T3-regulated genes from brain, limb, and tail, although more than 70% of T3-regulated genes are tissue-specific, likely due to the fact that not all genes are annotated into GO categories and that GO categories common to different organs also contain genes regulated by T3 tissue specifically. Finally, a core set of upregulated genes, most previously unknown to be T3-regulated, were identified and enriched in genes involved in transcription and cell signaling.

Animals↗

PubMed2006

Ranbezolid, a novel oxazolidinone antibacterial: in vivo characterisation of monoamine oxidase inhibitory potential in conscious rats.

Ranbezolid, a novel oxazolidinone antibacterial, competitively inhibits monoamine oxidase-A (MAO-A), in vitro. The consequences of MAO-A inhibition was evaluated in vivo, by testing interaction of Ranbezolid with tyramine (in solution or mixed with feed), and amine containing cold remedies on pressor response in conscious rats. Single and repeat doses of Ranbezolid (50 mg/kg, p.o.) did not affect pressor response to tyramine (5 or 15 mg/kg), but potentiated the same after a single dose of 100 mg/kg. Co-administration of Ranbezolid with tyramine in feed or with cold remedies also did not potentiate the respective pressor responses. These results suggest that Ranbezolid exhibits minimal cardiovascular liability associated with MAO-A inhibition.

Acetamides↗

PubMed2006

Gene expression changes at metamorphosis induced by thyroid hormone in Xenopus laevis tadpoles.

Thyroid hormone (TH) controlled gene expression profiles have been studied in the tail, hind limb and brain tissues during TH-induced and spontaneous Xenopus laevis metamorphosis. Amplified cRNA probes mixed with a universal standard were hybridized to a set of 21,807-sense strand 60-mer oligonucleotides on each slide representing the entries in X. laevis UniGene Build 48. Most of the up-regulated genes in hind limb and brain are the same. This reflects in part the fact that the initial response to TH induction in both tissues is cell proliferation. A large number of up-regulated genes in the limb and brain programs encode common components of the cell cycle, DNA and RNA metabolism, transcription and translation. Notch is one of the few genes that is differentially expressed exclusively in the brain in the first 48 h of TH induction studied in these experiments. The TH-induced gene expression changes in the tail are different from the limb and brain programs. Distinct muscle and fibroblast programs were identified in the tail. Dying muscle fibers in tail (marked by active caspase-3) up-regulate a group of genes that include proteolytic enzymes. At the climax of metamorphosis, tail muscle down-regulates more than half of the genes that encode the glycolytic enzymes in the cytoplasm and the tricarboxylic acid pathway and all five complexes of the electron transport system in mitochondria. These changes in gene expression precede the activation of caspase-3. Some of these same energy metabolism-related genes are up-regulated in the limb and brain programs by TH. A prominent feature of the tail fibroblasts is the down-regulation of several collagen and other extra cellular matrix genes and the up-regulation of hydrolytic enzymes that are responsible for dissolving the notochord and resorbing the tail.

Animals↗

PubMed2005

Synthesis and SAR of novel oxazolidinones: discovery of ranbezolid.

Novel oxazolidinones were synthesized containing a number of substituted five-membered heterocycles attached to the 'piperazinyl-phenyl-oxazolidinone' core of eperezolid. Further, the piperazine ring of the core was replaced by other diamino-heterocycles. These modifications led to several compounds with potent activity against a spectrum of resistant and susceptible gram-positive organisms, along with the identification of ranbezolid (RBx 7644) as a clinical candidate.

Animals↗

PubMed2005

Thyroid hormone controls multiple independent programs required for limb development in Xenopus laevis metamorphosis.

Thyroid hormone (TH) is required for limb development in Xenopus laevis. Specific cell types in the growing limb were targeted for expression of a dominant negative form of the TH receptor by sperm-mediated transgenesis. Limb muscle development, the innervation of muscle from the spinal cord, and cartilage growth can be inhibited without affecting patterning of the limb or differentiation of other cell types. Remodeling of the skin occurs late in metamorphosis after the limb has formed. The coordination of these independent programs is affected in part by the control that TH exerts over DNA replication in all cell types of the limb.

Animals↗

PubMed2004

New oxorhenium(V) complexes with 2N2S donor sets and radiochemical behavior of their technetium analogs.

Oxorhenium(V) complexes of two thioether amines have been synthesized and characterized spectroscopically. The five-coordinated ReO(3+) moiety is satisfied by the amine compounds behaving as dibasic tetradentate (NSSN) ligands and a chloride ion. The radioanalytical studies of their technetium analogs have been carried out at different pH values in the range 3-10. The solvent extraction, TLC, electrophoresis and HPLC studies using (99m)Tc radiotracer indicate that the labeled complex with the TcO(3+) core is similar to the rhenium complex with the ReO(3+) core.

Journal Article↗

PubMed2004

Controlling transgene expression to study Xenopus laevis metamorphosis.

Sperm-mediated transgenesis of Xenopus laevis is the first application of genetic methodology to an amphibian. However, some transgenes are lethal when they are expressed constitutively. To study the influence of these genes on amphibian metamorphosis and to generate F1 progeny from mature transgenic adults, these transgenes must be placed under the control of an inducible system so that they can be activated at specific times in development. We show that two well known binary inducible gene expression systems supplement transgenesis for the study of X. laevis metamorphosis, one system controlled by the progesterone analogue RU-486 and the other controlled by the tetracycline derivative doxycycline. By inducing a dominant negative form of the thyroid hormone receptor under the control of doxycycline specifically in the nervous system we have delimited the developmental periods within which thyroid hormone controls innervation of the developing limb from the spinal cord.

Animals↗

PubMed2002

Multiple thyroid hormone-induced muscle growth and death programs during metamorphosis in Xenopus laevis.

Xenopus laevis tadpole tails contain fast muscle fibers oriented in chevrons and two pairs of slow muscle "cords" along the length of the tail. When tail resorption is inhibited by a number of different treatments, fast muscle but not the slow cord muscle still is lost, demonstrating that the fast tail muscle is a direct target of the thyroid hormone-induced death program. Expression of a dominant negative form of the thyroid hormone receptor (TRDNalpha) was restricted to tadpole muscle by means of a muscle-specific promoter. Even though the transgene protects fast tail muscle from thyroid hormone (TH)-induced death, the tail shortens, and the distal muscle chevrons at the tail tip are degraded. This default pathway for muscle death is probably caused by the action of proteolytic enzymes secreted by neighboring fibroblasts. Non-muscle tissues that are sensitive to TH, such as the fibroblasts, are not protected by the transgene when it is expressed solely in muscle. If allowed to develop to metamorphosis, these transgenic animals die at the climax of metamorphosis before tail resorption has begun. Their limbs have very little muscle even though the rest of limb morphology is normal. Thus, fast tail muscle and limb muscle have their own cell autonomous death and growth programs, respectively, that are independent of the fate of the other neighboring cell types. In contrast, death of the slow muscle is controlled by the other cell types of the tail.

Animals↗