Search PubMed⌕ Search

Biomedical subjects

M Zuker

Publications and source records attributed to M Zuker.

50 records · Page 3Linked to original sources
PubMed1984

Some simple computational methods to improve the folding of large RNAs.

Computational methods are described which increase the efficiency of the RNA folding algorithm described by Zuker and Stiegler. Bit addressing has been used to reduce the memory requirements from 2NxN to NxN/2. The order in which the nucleotide sequence is examined internally has been altered, and some additional short arrays which carry temporary information have been introduced. These changes optimize the management of the large data arrays generated by the algorithm. The methods were developed for use with a UNIVAC 1100/82 computer. They are, however, easily adaptable to other computers; especially those with virtual memory capabilities. The analysis of sequences up to 1000 nucleotides long are relatively routine, and larger searches are also feasible. Some limitations and applications of the algorithm are also discussed.

Base Sequence↗
PubMed1983

Self-association of the cardiac fatty acid binding protein. Influence on membrane-bound, fatty acid dependent enzymes.

The present study on the fatty acid binding protein, purified from pig heart and studied by three independent techniques (electron spin resonance, circular dichroism, and polyacrylamide gel electrophoresis), suggests that the protein self-aggregates and exists in at least four distinct molecular species. This plurality is demonstrated by the presence of four bands after electrophoretic migration at pH 7.2 and by three transitions of molar ellipticity theta 225 that depend on protein concentration. A mathematical model is formulated to simulate the three transitions and to calculate the concentrations of the four species. The multistates manifest themselves in a complex binding capacity for fatty acid, with two sigmoidal components in the binding curve. A general equation for the curve is formulated, and the characteristic constants are evaluated by a nonlinear least-squares fit. The experimental results and their interpretation in quantitative terms lead to a theoretical evaluation of the importance of this new property of self-aggregation of the protein on the activity of membrane-bound model enzymes which are fatty acid or acyl coenzyme A dependent.

Animals↗
PubMed1983

Secondary structure of the Tetrahymena ribosomal RNA intervening sequence: structural homology with fungal mitochondrial intervening sequences.

Splicing of the ribosomal RNA precursor of Tetrahymena is an autocatalytic reaction, requiring no enzyme or other protein in vitro. The structure of the intervening sequence (IVS) appears to direct the cleavage/ligation reactions involved in pre-rRNA splicing and IVS cyclization. We have probed this structure by treating the linear excised IVS RNA under nondenaturing conditions with various single- and double-strand-specific nucleases and then mapping the cleavage sites by using sequencing gel electrophoresis. A computer program was then used to predict the lowest-free-energy secondary structure consistent with the nuclease cleavage data. The resulting structure is appealing in that the ends of the IVS are in proximity; thus, the IVS can help align the adjacent coding regions (exons) for ligation, and IVS cyclization can occur. The Tetrahymena IVS has several sequences in common with those of fungal mitochondrial mRNA and rRNA IVSs, sequences that by genetic analysis are known to be important cis-acting elements for splicing of the mitochondrial RNAs. In the predicted structure of the Tetrahymena IVS, these sequences interact in a pairwise manner similar to that postulated for the mitochondrial IVSs. These findings suggest a common origin of some nuclear and mitochondrial introns and common elements in the mechanism of their splicing.

Base Sequence↗
PubMed1982

Structure-function relationship of Rous sarcoma virus leader RNA.

Cells infected by RSV synthesize viral 35S RNA as well as subgenomic 28S and 22S RNAs coding for the Env and Src genes respectively. In addition, at least the 5' 101 nucleotides of the leader are also conserved and we have shown previously that this sequence contains a strong ribosome binding site (J.-L. Darlix et al., J. Virol. 29, 597). We now report the RNA sequence of Rous Sarcoma virus (RSV) leader RNA and propose a folding of this 5' untranslated region which brings the Cap, the initiation codon for Gag and the strong ribosome binding site close to each other. We also show that ribosomes protect a sequence just upstream from initiator Aug of Gag in vitro, and believed to interact with part of the strong ribosome binding site according to the folding proposed for the leader RNA.

Animals↗
PubMed1982

Heterogeneity of the sympathetic innervation of rat interscapular brown adipose tissue via intercostal nerves.

The interscapular brown adipose tissue (IBAT) of cold-acclimated white rats was partially denervated by cutting in most cases four of the five intercostal nerves going to one of its two bilaterally located, lobular pads. After 24 h the functional ability and the degree of residual sympathetic innervation of the pads and of their lobes were assessed (in separate groups of rats): the former by measuring tissue blood flow as an index of sympathetically mediated calorigenesis during exposure of the animals to -6 degrees C, the latter by measuring the residual noradrenaline (NA) content of the tissue. Only the four anterior intercostal nerves contributed significantly to the sympathetic innervation of IBAT pads. On average their contributions were unequal, but there was considerable variation between rats in the relative contribution of each nerve. The measurements on lobes of the pads indicated that the sympathetic fibers supplied by a given intercostal nerve were not distributed uniformly throughout the pad. For example, measurements of NA indicated that on average the fibers of the fourth nerve were four times as abundant in the lateral lobe as in the posterior lobe. But at this level of analysis also there was wide variation between rats. The variation in the participation of each intercostal nerve in the sympathetic innervation of rat IBAT and in the distribution of each nerve's fibers to different parts of the IBAT pad could be of genetic origin or it could reflect a considerable degree of flexibility during development of the innervation of IBAT. Because of the observation variation, it is suggested that if functional responses of IBAT evoked by electrical stimulation of intercostal nerves are to be recorded from a highly localized area of tissue, stimulation of all the nerves probably would be required to obtain responses that are consistent between animals.

Adipose Tissue, Brown↗
PubMed1981

Structural organization of the 16S ribosomal RNA from E. coli. Topography and secondary structure.

Extensive studies in our laboratory using different ribonucleases resulted in valuable data on the topography of the E.coli 16S ribosomal RNA within the native 30S subunit, within partially unfolded 30S subunits, in the free state, and in association with individual ribosomal proteins. Such studies have precise details on the accessibility of certain residues and delineated highly accessible RNA regions. Furthermore, they provided evidence that the 16S rRNA is organized in its subunit into four distinct domains. A secondary structure model of the E.coli 16S rRNA has been derived from these topographical data. Additional information from comparative sequence analyses of the small ribosomal subunit RNAs from other species sequenced so far has been used.

Computers↗
PubMed1981

Optimal computer folding of large RNA sequences using thermodynamics and auxiliary information.

This paper presents a new computer method for folding an RNA molecule that finds a conformation of minimum free energy using published values of stacking and destabilizing energies. It is based on a dynamic programming algorithm from applied mathematics, and is much more efficient, faster, and can fold larger molecules than procedures which have appeared up to now in the biological literature. Its power is demonstrated in the folding of a 459 nucleotide immunoglobulin gamma 1 heavy chain messenger RNA fragment. We go beyond the basic method to show how to incorporate additional information into the algorithm. This includes data on chemical reactivity and enzyme susceptibility. We illustrate this with the folding of two large fragments from the 16S ribosomal RNA of Escherichia coli.

Base Composition↗
PubMed1980

[Secondary and topographic structure of ribosomal RNA 16S of Escherichia coli].

We present a model for the secondary structure of 16S ribosomal RNA from E. coli. This model has been deduced by restricting the total number of theoretical base pairings using the following criteria: (1) susceptibility of residues towards enzymatic probes that are specific for either paired or single stranded regions; (2) reactivity of certain residues to chemical modification; (3) evidence for medium and long range interactions; (4) comparative analysis of ribosomal RNA sequences from other organisms.

Base Sequence↗
PubMed1980

The measurement of rectal and testis temperature in conscious mice, with observations on the effect of direct heating.

The application of Newton's law of cooling to freshly killed mice was found not to measure accurately their rectal or testis temperature. Improvements in the fitting process gave satisfactory results for rectal temperature only. A diffusion model was applied to testis cooling but was of no avail. Finally a satisfactory correction factor was determined empirically. This method was applied to conscious mice whose hindquarters were immersed in a stirred oilbath at 34 to 42 degrees C for 1 h, and to controls. It was found that both rectal and testis temperatures increased with bath temperature, producing a graph with a slope of only 0.5, indicating a regulatory capacity. Conscious mice, but not anaesthetised, can maintain a testis temperature of 39 degrees C in a bath at 42 degrees C.

Animals↗
PubMed1977

Equivalency of linear least squares curve fitting and reciprocal functions in protein circular dichroic spectra analysis.

Two methods for the analysis of the circular dichroism spectra of proteins for determination of secondary structure have been examined. These are the linear curve fitting of the data, minimized in the least squares sense, and the method of reciprocal functions proposed by C.C. Baker and I. Isenberg, Biochemistry 15 (1976) 629. It is shown that the use of these two methods give results that are identical, providing the same set of reference spectra are used in each case, and, therefore, that no new information is obtained by the use of either one over the other.

Bacterial Proteins↗
PubMedDate not supplied

Metrics on RNA secondary structures.

Many different programs have been developed for the prediction of the secondary structure of an RNA sequence. Some of these programs generate an ensemble of structures, all of which have free energy close to that of the optimal structure, making it important to be able to quantify how similar these different structures are. To deal with this problem, we define a new class of metrics, the mountain metrics, on the set of RNA secondary structures of a fixed length. We compare properties of these metrics with other well known metrics on RNA secondary structures. We also study some global and local properties of these metrics.

Biometry↗