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Biomedical subjects

T M Nair

Publications and source records attributed to T M Nair.

13 recordsLinked to original sources
PubMed2004

A database designed to computationally aid an experimental approach to alternative splicing.

A unique microarray approach has been developed to profile alternative splicing in the cell. To support the development of this approach, we have developed the Manually Annotated Alternatively Spliced Events (MAASE) database system, which is a unique alternative splicing information resource designed specifically with experimentalists in mind. MAASE is an online resource for the convenient access, identification, and annotation of alternative splicing events (ASEs). MAASE consists of two components: an annotation system and a curated database. The annotation system is a web-based workspace that combines manual and computational approaches to identifying and annotating ASEs, a combination that is vital if a comprehensive collection is to be obtained. The annotation system is publicly available and provides a scalable solution to acquiring as well as contributing to annotated ASEs. MAASE annotated ASEs are deposited into the database component, which can either be queried one entry at a time or multiple entries at a time with convenient access to alternatively spliced junctional and surrounding sequences to facilitate the design of microarray experiments.

Alternative Splicing↗
PubMed2000

Surface plasmon resonance kinetic studies of the HIV TAR RNA kissing hairpin complex and its stabilization by 2-thiouridine modification.

Surface plasmon resonance (BIACORE) was used to determine the kinetic values for formation of the HIV TAR-TAR* ('kissing hairpin') RNA complex. The TAR component was also synthesized with the modified nucleoside 2-thiouridine at position 7 in the loop and the kinetics and equilibrium dissociation constants compared with the unmodified TAR hairpin. The BIACORE data show an equilibrium dissociation constant of 1.58 nM for the complex containing the s(2)U modified TAR hairpin, which is 8-fold lower than for the parent hairpin (12.5 nM). This is a result of a 2-fold faster k(a) (4.14x10(5) M(-1) s(-1) versus 2.1x10(5) M(-1) s(-1)) and a 4-fold slower k(d) (6.55x10(-4) s(-1) versus 2.63x10(-3) s(-1)). (1)H NMR imino spectra show that the secondary structure interactions involved in complex formation are retained in the s(2)U-modified complex. Magnesium has been reported to significantly stabilize the TAR-TAR* complex and we found that Mn(2+) and Ca(2+) are also strongly stabilizing, while Mg(2+) exhibited the greatest effect on the complex kinetics. The stabilizing effects of 2-thiouridine indicate that this base modification may be generally useful as an antisense RNA modification for oligonucleotide therapeutics which target RNA loops.

Calcium↗
PubMed1999

External hydrocephalus in primary hypomagnesaemia: a new finding.

This paper reports a new finding in two siblings with primary hypomagnesaemia as a result of renal magnesium wasting, namely, rapidly increasing head size. External hydrocephalus and brain shrinkage in primary hypomagnesaemia seen on computed tomography of the brain with reversibility after magnesium treatment has not been reported previously.

Female↗
PubMed1998

Evidence for intrinsic DNA bends within the human cdc2 promoter.

Cyclin-dependent protein kinases (Cdks) are key regulatory proteins of the eukaryotic cell cycle. The product of the cdc2 gene, p34cdc2 (cdk1), is the catalytic subunit of a serine/ threonine protein kinase that is expressed in S phase and functions in the G2 to M phase transition. Previous studies indicate that the human cdc2 gene expression is dependent on cell growth, and is transcriptionally regulated in a complex manner involving multiple transcription factors binding to specific sites in the promoter. One possible mechanism by which these transcription factors regulate transcription is that by binding to their cognate sites they induce bends in the DNA helix, thereby allowing their interaction with the basal transcription machinery through protein-protein contacts. Such protein-induced DNA bending is also influenced by intrinsic bends in the regulatory region. Using both theoretical and experimental approaches, the study reports that the human cdc2 promoter has an intrinsic DNA bend with a broad locus of curvature.

CDC2 Protein Kinase↗
PubMed1997

Calliper randomization: an artificial neural network based analysis of E. coli ribosome binding sites.

An artificial neural network based approach has been used in analyzing the translation initiation region of E. coli. The approach is based on using a trained network capable of recognizing a particular region and presenting the network with randomized calliper inputs of the true sequence. The network responds with an error when the regions which have been the main source of knowledge are randomized. Analysis of the E. coli ribosome binding sites using this approach reveal that the initiation codon and the Shine/Dalgarno sequence which are known to be important for translation initiation are also important in imparting knowledge to the network. Further, selectively changing the usually occurring initiation codon AUG, to GUG, UUG and AUU, which occur less frequently, decreases the network performance in accordance with the frequency of their occurrence. This approach can be used as a general method to derive consensus.

Binding Sites↗
PubMed1996

Theoretical permutation gel electrophoretic analysis of a curved DNA fragment located in circular permutation.

Using the theoretical model for DNA curvature, we analyzed a set of fragments with a curved insert located in circular permutation. The theoretical permutation analysis of each of the cyclically located fragments reveals the presence of a shifting molecular bend locus. The delineation of the molecular bend locus associated with the fragments obtained by a second permutation helps in providing an explanation for the differential mobility behavior of the fragments.

Animals↗
PubMed1995

Differential binding of RNA polymerase to the wild type Mu mom promoter and its C independent mutant: a theoretical analysis.

Using the theoretical model for DNA bending we have analyzed the Mu mom promoter wild type and its mutant tin7 which showed differential binding to the RNA polymerase. We have demonstrated here the structural change as a result of the point mutation which may be responsible for the altered binding of RNA polymerase. Analysis using both sets of parameters essentially gives the same result.

Bacteriophage mu↗
PubMed1995

Analysis of transcription control signals using artificial neural networks.

The role of the upstream region in controlling the transcription efficiency of a gene is well established. However, the question of predicting the extent of gene expressed given the upstream region has so far remained unresolved. Using an artificial neural network (ANN) to capture the internal representation associated with the transcription control signal, the present work predicts the rate of mRNA synthesis based on the pattern contained in the upstream region. Further, the model has been used to predict the transcription efficiency for all possible single base mutations associated with the beta-globin promoter. The simulation results reveal that apart from the experimental observation that alpha-79G-A and -78G-A mutation increases the efficiency of transcription, mutation in these regions by C or T also causes an increase in transcription. Furthermore the simulation results verify that mutations in the conserved region, in general, decrease the transcriptional efficiency. However, the results also show that certain sequence elements, when mutated, either cause a marginal increase in the level of transcription or have no effect on transcription levels. The simulation results can be used as a guide in designing mutation experiments since an a priori estimate of the possible outcome of a mutation can be obtained.

Animals↗
PubMed1994

On the mobility behavior of a curved DNA fragment located in circular permutation.

Experimental and theoretical investigations on the mobility behavior of a set of permuted fragments with a K-DNA insert is reported. The fragments with the permuted flanking sequences have the K-DNA insert located differentially with respect to the fragment ends. The fragment wherein the insert is located in the center showed maximum retardation as compared to fragments where the insert was at the end. The experimental analysis is also in accord with the theoretical investigation.

Base Sequence↗
PubMed1994

Application of artificial neural networks for prokaryotic transcription terminator prediction.

Artificial neural networks (ANN) to predict terminator sequences, based on a feed-forward architecture and trained using the error back propagation technique, have been developed. The network uses two different methods for coding nucleotide sequences. In one the nucleotide bases are coded in binary while the other uses the electron-ion interaction potential values (EIIP) of the nucleotide bases. The latter strategy is new, property based and substantially reduces the network size. The prediction capacity of the artificial neural network using both coding strategies is more than 95%.

DNA↗
PubMed1994

On the consensus structure within the E. coli promoters.

Using the theoretical model of DNA curvature, we have studied about 112 different E. coli promoters with a view to obtain some common super structures associated with them. Out of the 112 promoters analyzed by theoretical gel electrophoresis permutation about 66 of them have their minima lying between the -10 and the -35 region. The analysis of the bases at the minima reveals strong structural similarities. The differences can account for the varying strengths of the promoters as well as for different degree with which the RNA polymerase binds to these regions. The effects of mutation in each of these 112 promoters and their changes in curvature dispersion have also been evaluated.

Consensus Sequence↗