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PubMed2002

Integrating historical and mechanistic biology enhances the study of adaptation.

Adding a causal, mechanistic dimension to the study of character evolution will increase the strength of inferences regarding the evolutionary history of characters and their adaptive consequences. This approach has the advantage of illuminating mechanism and testing evolutionary hypotheses rigorously. We consider the advantages of combining mechanistic and historical biology in the study of behavior, physiology, and development. We present six examples to illustrate the advantages: (1) preexisting biases in sound perception in frogs; (2) preexisting biases in visual cues in swordtailfishes; (3) exploitation of prey location behavior for attraction of mates in water mites; (4) heterospecific mating in asexual molly fishes; (5) developmental foundation of morphological diversification in amphibian digits; and (6) locomotor performance at low temperature and the evolution of nocturnality in geckos. In each of these examples, the dominant role of history, combined with organismal integration, makes ignoring history a risky proposition.

Adaptation, Physiological↗
PubMed1992

Biology of Rous sarcoma virus adapted for replication and transformation of duck cells.

A duck-adapted variant of the Prague strain of Rous sarcoma virus and its molecularly cloned derivatives were characterized biologically. The virus replicated and transformed with the same efficiency both duck and chicken embryo fibroblasts. The daPR-RSV-C was also used for induction of tumours in newborn hamsters. The virus from virogenic hamster tumours could be rescued using the duck cells as indicator cells. The virus rescue was influenced by restricted replication of the virus in the indicator cells.

Animals↗
PubMed2001

Humans as the world's greatest evolutionary force.

In addition to altering global ecology, technology and human population growth also affect evolutionary trajectories, dramatically accelerating evolutionary change in other species, especially in commercially important, pest, and disease organisms. Such changes are apparent in antibiotic and human immunodeficiency virus (HIV) resistance to drugs, plant and insect resistance to pesticides, rapid changes in invasive species, life-history change in commercial fisheries, and pest adaptation to biological engineering products. This accelerated evolution costs at least $33 billion to $50 billion a year in the United States. Slowing and controlling arms races in disease and pest management have been successful in diverse ecological and economic systems, illustrating how applied evolutionary principles can help reduce the impact of humankind on evolution.

Adaptation, Physiological↗
PubMed2005

Identification of a novel small-molecule inhibitor of the hypoxia-inducible factor 1 pathway.

Hypoxia-inducible factor 1 (HIF-1) is the central mediator of cellular responses to low oxygen and has recently become an important therapeutic target for solid tumor therapy. Inhibition of HIF-1 is expected to result in the attenuation of hypoxia-inducible genes, which are vital to many aspects of tumor biology, including adaptative responses for survival under anaerobic conditions. To identify small molecules inhibiting the HIF-1 pathway, we did a biological screen on a 10,000-membered natural product-like combinatorial library. The compounds of the library, which share a 2,2-dimethylbenzopyran structural motif, were tested for their ability to inhibit the hypoxic activation of an alkaline phosphatase reporter gene under the control of hypoxia-responsive elements in human glioma cells. This effort led to the discovery of 103D5R, a novel small-molecule inhibitor of HIF-1alpha. 103D5R markedly decreased HIF-1alpha protein levels induced by hypoxia or cobaltous ions in a dose- and time-dependent manner, whereas minimally affecting global cellular protein expression levels, including that of control proteins such as HIF-1beta, IkappaBalpha, and beta-actin. The inhibitory activity of 103D5R against HIF-1alpha was clearly shown under normoxia and hypoxia in cells derived from different cancer types, including glioma, prostate, and breast cancers. This inhibition prevented the activation of HIF-1 target genes under hypoxia such as vascular endothelial growth factor (VEGF) and glucose transporter-1 (Glut-1). Investigations into the molecular mechanism showed that 103D5R strongly reduced HIF-1alpha protein synthesis, whereas HIF-1alpha mRNA levels and HIF-1alpha degradation were not affected. 103D5R inhibited the phosphorylation of Akt, Erk1/2, and stress-activated protein kinase/c-jun-NH(2)-kinase, without changing the total levels of these proteins. Further studies on the mechanism of action of 103D5R will likely provide new insights into its validity/applicability for the pharmacologic targeting of HIF-1alpha for therapeutic purposes.

Benzopyrans↗
PubMed1979

Recursive evolution.

In evolutionary systems in which the units (individuals) are generated by a morphogenetic process, unbiased "mosaic type" mutability of the phenotype is not possible (Waddington's principle). The question is whether this unavoidable "channeling" can itself be made plastic through provision of alternative morphogeneses possessing differing "hot spots." If so, plasticity would not only be reestablished, but be established at a higher level. Plasticity itself would be plastic. The property of ultrasplasticity is evolutionarily necessary and stable, but perhaps not possible. Ultraplastic systems form a subclass of "temporal brains" as described in deductive biology. Many of their properties have yet to be discovered.

Adaptation, Biological↗
PubMed2005

The rate of compensatory mutation in the DNA bacteriophage phiX174.

A compensatory mutation occurs when the fitness loss caused by one mutation is remedied by its epistatic interaction with a second mutation at a different site in the genome. This poorly understood biological phenomenon has important implications, not only for the evolutionary consequences of mutation, but also for the genetic complexity of adaptation. We have carried out the first direct experimental measurement of the average rate of compensatory mutation. An arbitrary selection of 21 missense substitutions with deleterious effects on fitness was introduced by site-directed mutagenesis into the bacteriophage phiX174. For each deleterious mutation, we evolved 8-16 replicate populations to determine the frequency at which a compensatory mutation, instead of the back mutation, was acquired to recover fitness. The overall frequency of compensatory mutation was approximately 70%. Deleterious mutations that were more severe were significantly more likely to be compensated for. Furthermore, experimental reversion of deleterious mutations revealed that compensatory mutations have deleterious effects in a wild-type background. A large diversity of intragenic compensatory mutations was identified from sequencing fitness-recovering genotypes. Subsequent analyses of intragenic mutation diversity revealed a significant degree of clustering around the deleterious mutation in the linear sequence and also within folded protein structures. Moreover, a likelihood analysis of mutation diversity predicts that, on average, a deleterious mutation can be compensated by about nine different intragenic compensatory mutations. We estimate that about half of all compensatory mutations are located extragenically in this organism.

Adaptation, Biological↗
PubMed1982

Conformational activation of aminoacyl-tRNA synthetases upon binding of tRNA. A facet of a multi-step adaptation process leading to the optimal biological activity.

The activation of the catalytic center of aminoacyl-tRNA synthetases upon binding of the tRNA, previously reported in the case of yeast phenylalanyl-tRNA and valyl-tRNA synthetases [Renaud et al., (1981) Proc. Natl Acad. Sci. USA, 78, 1606-1608] has been investigated in other systems. It is shown that this property is encountered not only in cognate systems (phenylalanyl, valyl and arginyl) but also in the non-cognate systems which are particularly efficient in misaminoacylation reactions. The arginyl system, the peculiarity of which is to form the aminoacyladenylate only in the presence of the cognate tRNA, is shown to be a border-line case of this general process of catalytic center activation. In the case of the phenylalanyl system, the crucial role of the wybutine residue (adjacent to the anticodon) in the activation of phenylalanyl-tRNA synthetase by the tRNA core has been analysed by comparison with native or modified non-cognate tRNAs (tRNATyr, tRNAArg). It is proposed that upon complex formation between a tRNA and its cognate aminoacyl-tRNA synthetase, a multistep adaptation process takes place in order to promote the optimal rate for the aminoacylation reaction, thus contributing to the specificity of this reaction.

Adaptation, Biological↗
PubMed2000

Adapting atomic force microscopy for cell biology.

We present details of our AFM modifications to produce an adaptable imaging system for the cell biologist. We have designed and validated a new inverted microscope interface and a scan head with increased Z-range, based upon the TopoMetrix Explorer AFM. We have utilised these changes, together with home-made glass ball cantilevers, to obtain topographical information over cells with large Z-dimension (over 15 microm high), and mapped calcitonin-calcitonin receptor binding forces in living bone cells. We conclude that modified AFM can be used to evaluate intermolecular events in living cells and that this approach will ensure general application to the study of receptor-ligand interactions under truly physiological conditions.

Animals↗
PubMed2002

Analysis of certain tranquilizers in biological fluids.

A review with 282 references is presented that deals with the reported methods of analysis of phenothiazines, thioxanthenes, and benzodiazepine derivatives of pharmaceutical interest. The review includes the methods adapted in biological fluids.

Animals↗
PubMed2004

Rupert Riedl and the re-synthesis of evolutionary and developmental biology: body plans and evolvability.

This paper reviews the scientific career of Rupert Riedl and his contributions to evolutionary biology. Rupert Riedl, a native of Vienna, Austria, began his career as a marine biologist who made important contributions to the systematics and anatomy of major invertebrate groups, as well as to marine ecology. When he assumed a professorship at the University of North Carolina in 1968, the predominant thinking in evolutionary biology focused on population genetics, to the virtual exclusion of most of the rest of biology. In this atmosphere Riedl developed his "systems theory" of evolution, which emphasizes the role of functional and developmental integration in limiting and enabling adaptive evolution by natural selection. The main objective of this theory is to account for the observed patterns of morphological evolution, such as the conservation of body plans. In contrast to other "alternative" theories of evolution, Riedl never denied the importance of natural selection as the driving force of evolution, but thought it necessary to contextualize natural selection with the organismal boundary conditions of adaptation. In Riedl's view development is the most important factor besides natural selection in shaping the pattern and processes of morphological evolution.

Adaptation, Biological↗
PubMed2004

Incompatible mechanical properties in compact bone.

The covariation of a number of mechanical of properties, and some physical characteristics, of compact bones from a wide range of bones were examined. Young's modulus was well predicted by a combination of mineral content and porosity. Increasing Young's modulus was associated with: increasing stress at yield, increasing bending strength, and a somewhat higher resilience, tensile strength and fatigue strength. Contrarily, in the post-yield region a higher Young's modulus (and more clearly, a higher mineral content) was associated with: a reduced work to fracture in tension, a reduced impact strength and an increased notch sensitivity in impact. Increasing porosity is associated with deleterious effects in the pre-yield region, but has little effect in the post-yield region. Bone, like many other materials, is unable to have good qualities in both the pre- and post-yield regions. Since an increase in mineral or Young's modulus is more potent, that is deleterious, in the post-yield than it is advantageous in the pre-yield region, it is likely that mineral content will be selected to be slightly lower than would be the case if it were equally potent in both regions. As is usual in biology, different adaptive extremes are incompatible.

Animals↗