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Biomedical subjects

H M Martinez

Publications and source records attributed to H M Martinez.

7 recordsLinked to original sources

Detecting pseudoknots and other local base-pairing structures in RNA sequences.

The current version of RNAFOLD now has the capability for conducting comparative studies relative to nonbifurcating hairpins contained in the global structures produced by the dynamic programming and Monte Carlo methods. It also has the capability of both finding and comparing hairpins and pseudoknots independently of global structures. The efficacy of these increased capabilities has been tested for select families of sequences, and the results thus far indicate favorable utility. Under consideration is a further extension designed to incorporate pseudoknots within global structures. Written in the C language, RNAFOLD and its companion program, GENALIGN, for doing multiple alignments in the comparison of pseudoknots and hairpins, is available for UNIX systems on standard 1/2-inch, 9-track tape or on SUN tape cartridges.

Base Sequence

An RNA secondary structure workbench.

A multiple approach to the study of RNA secondary structure is described which provides for the independent drawing of structures using base-pairing lists, for the generation of local structures in the form of hairpins, and for the generation of global structures by both Monte Carlo and dynamic programming methodologies. User-adjustable parameters provide for limiting the size of hairpin loops, bulges and inner loops, and constraints can be imposed relative to position-dependent base pairing.

Algorithms

An automaton analogue of unicellularity.

There is presented in outline form an abstract model of a cell in an evolutionary context. The design is based on an elaboration of John Holland's one-dimensional, abstract universe recently posed for the study of the emergence of self-replicating systems. Eight new ingredients constitute the elaboration. They suggest how compartmentation of a set of "molecules" in a one-dimensional universe can be achieved and how a suitable, compartmentalized set of molecules can replicate in a manner analogous to real cell replication, i.e., there is segregation and semi-conservative replication of the genetic material, and there is division of the compartment through the construction of an "inner membrane". The approach to self-replication of a spatially delimited entity exemplified by this design differs from the abstract models of replication of the von Neumann or Laing type. In these the replicating entity constructs a copy external to itself and does not undergo any essential replacement of any of its parts. Also, while in these models the concern is primarily with questions of the "logical" type, our design has in mind features identifiable with both energy and information considerations. Thus, the rules which define the underlying "physics and chemistry" imply that the self-replicating entity is a dissipative structure. A constant flux of energy is required to maintain the system far from thermodynamic equilibrium in order to account for multiple steady states, and hence dynamic structure.

Cell Compartmentation

Synchronized ultradian cortisol rhythms in monkeys: persistence during corticotropin infusion.

A highly synchronized ultradian cortisol rhythm with a predominant periodicity of 85 to 90 minutes was observed in eight isolated monkeys; this rhythm may be harmonically related to the circadian rhythm. The persistence of this synchronized rhythm during supramaximal infusions of adrenocorticotropin not only suggests that feedback is not causative but also challenges the classic concept that bursts of cortisol secretion are dependent upon an immediately preceding release of adrenocorticotropin.

Adrenocorticotropic Hormone

Interaction of glucocorticoid receptor-steroid complexes with acceptor sites.

The binding of the "activated" receptor-glucocorticoid complexes of cultured rat hepatoma cells to nuclei, chromatin, and DNA has been studied under cell-free conditions. A critical factor in determining the shape of the binding curve is shown to be an inhibitory material which is present in crude cytosol and which can be removed without destroying the receptor-steroid complex. These and other results argue that the apparent saturation observed in earlier experiments may have been due to the inhibitors. Thus, the actual number of acceptor sites in hepatoma tissue culture cell nuclei is much larger than previously estimated and their affinity for the complex is lower. Nuclear binding experiments indicate that the inhibitory material interacts with the receptor-steroid complex. The inhibitors appear to be macromolecular; but their effects cannot be mimicked by albumin or hemoglobin. The acceptor capacity at low ionic strength for binding receptor-glucocorticoid complexes increases when proceeding from nuclei to DNA. An analysis of the kinetics of association and dissociation and of the relative binding behavior of nuclei and DNA argues that the affinity of complex for nuclei is much greater than for DNA. DNA-associated histones reduce the amount of complex that binds to DNA. These and perhaps other chromosomal proteins may be responsible for the ordering of acceptor capacity. Evidence is presented that the difference in affinities of nuclear and DNA acceptors could also be due to chromosomal proteins. In nuclei, these proteins may thus both reduce the amount of complex binding by rendering regions of DNA less accessible and increase the binding affinity of some, or all, of those DNA binding sites which remain exposed.

Binding Sites

Polyamine metabolism in a rat brain tumor cell line: its relationship to the growth rate.

To investigate whether the metabolism of the polyamines putrescine, spermidine and spermine is related to cellular growth rate, we have measured the activities of L-ornithine decarboxylase and S-adenosyl-L-methionine decarboxylase as well as the levels of the polyamines in rat brain tumor cells at various stages of a 7-day in vitro growth period and correlated them with the continuous changes in specific growth rate ([dN[t]/dt]/N[t]). L-Ornithine decarboxylase and S-adenosyl-L-methionine decarboxylase both exhibited their maximal activities at the time of most rapid growth. A high positive correlation between the activities of these enzymes and the specific growth rate of the tumor cells during the entire growth period was demonstrated statistically. The pattern of fluctuation of the spermidine content during the culture cycle was similar to those of the enzyme activities and likewise showed a high positive correlation with the specific growth rate of the tumor cells during the entire growth period. The putrescine content exhibited a low positive correlation, whereas the spermine content exhibited a somewhat higher, but negative correlation with the specific growth rate. The high correlation between the specific growth rate of the tumor cells and the synthesis of the polyamines indicates that these events are primarily associated with processes involved in cell replication. Putrescine and spermidine are thought to participate in the regulation of cellular growth rate; a high content may augment, and a low content may restrain, cellular growth rate.

Adenosylmethionine Decarboxylase