Science and the 'emancipation of the mind': dreams, the mind, and slavery.

Dreams were a subject of interest to philosophers thinking about the connection between the mind and the body in the nineteenth century. Many scholars have pointed out that the mind and the body were intimately linked and affected each other. Although science was on its way to becoming more technical and numbers focused in its investigatory practices, medical students and other physician-philosophers investigated the nature of sleep and dreams. Medical students and advanced researchers speculated on the nature of consciousness and mused on where the mind travels to during the sleep processes. Other romantic figures like Dr Polydori speculated on the nature of sleep walking in their medical dissertations. Dreams also had a powerful moral and motivational component, as dreams and activities in dreams, drove people like Benjamin Rush to embrace abolition. Other promoters of abolition used the nature of dreams to discusses the dreadfulness and suffering of slavery.

'The voice of the stomach': the mind, hypochondriasis and theories of dyspepsia in the nineteenth century.

Physicians and surgeons during the nineteenth century were eager to explore the causes of stomach and intestinal illnesses. Theories abounded that there was a sympathy between the mind and the body, especially in the case of the dyspepsia. The body was thought to have physical symptoms from the reactions of the mind, especially in the case of hypochondriasis. Digestive problems had a mental component, but mental anguish could also result from physical problems. Dissertations from aspiring as well as established physicians probed the mental causes of irritable bowel diseases and other diseases in the medical literature. Healing was thought to come from contextualizing the link between the problems of the mind and the resulting physical problems of the body.

The interplay between binding energy and catalysis in the evolution of a catalytic antibody.

Antibody catalysis provides an opportunity to examine the evolution of binding energy and its relation to catalytic function in a system that has many parallels with natural enzymes. Here we report such a study involving an antibody AZ-28 that catalyses an oxy-Cope rearrangement, a pericyclic reaction that belongs to a well studied and widely used class of reactions in organic chemistry. Immunization with transition state analogue 1 results in a germline-encoded antibody that catalyses the rearrangement of hexadiene 2 to aldehyde 3 with a rate approaching that of a related pericyclic reaction catalysed by the enzyme chorismate mutase. Affinity maturation gives antibody AZ-28, which has six amino acid substitutions, one of which results in a decrease in catalytic rate. To understand the relationship between binding and catalytic rate in this system we characterized a series of active-site mutants and determined the three-dimensional crystal structure of the complex of AZ-28 with the transition state analogue. This analysis indicates that the activation energy depends on a complex balance of several stereoelectronic effects which are controlled by an extensive network of binding interactions in the active site. Thus in this instance the combinatorial diversity of the immune system provided both an efficient catalyst for a reaction where no enzyme is known, as well as an opportunity to explore the mechanisms and evolution of biological catalysis.

Antibody catalysis of pericyclic reactions.

In an effort to increase our insight into the catalysis of pericyclic reactions we have initiated a detailed study of an antibody that catalyzes an oxy-Cope rearrangement. We have determined the stereochemistry of the antibody-catalyzed reaction, and experiments are in progress to determine the conformation of the substrate bound in the antibody combining site. The genes encoding the variable regions of this antibody have been cloned and sequenced, and we have made use of a bacterial expression system to produce this antibody as a Fab fragment in recombinant form, making it amenable to genetic manipulations such as site-directed mutagenesis. The recombinant Fab fragment has been crystallized in the presence of its transition state analog, and we are now in the process of determining its active site structure.

Adsorption to ice of fish antifreeze glycopeptides 7 and 8.

Experimental results show that fish antifreeze glycopeptides (AFGPs) 8 and 7 (with 4 and 5 repeats respectively of the Ala-Ala-Thr backbone sequence) bond onto ice prism planes aligned along a-axes, and inhibit crystal growth on prism planes and on surfaces close to that orientation. The 9.31-A repeat spacing of the AFGP in the polyproline II helix configuration, deduced from NMR studies, matches twice the repeat spacing of ice in the deduced alignment direction, 9.038 A, within 3%. A specific binding model is proposed for the AFGP and for the alpha-helical antifreeze peptide of winter flounder. For AFGP 7-8, two hydroxyl groups of each disaccharide (one disaccharide is attached to each threonine) reside within the ice surface, so that they are shared between the ice crystal and the disaccharide. This provides 24 hydrogen bonds between AFGP 8 and the ice and 30 for AFGP 7, explaining why the chemical adsorption is virtually irreversible and the crystal growth can be stopped virtually completely. The same scheme of sharing polar groups with the ice works well with the alpha-helical antifreeze of winter flounder, for which an amide as well as several hydroxyls are shared. The sharing of polar groups with the ice crystal, rather than hydrogen-bonding to the ice surface, may be a general requirement for adsoprtion-inhibition of freezing.

Relationships among Isoprene Emission Rate, Photosynthesis, and Isoprene Synthase Activity as Influenced by Temperature.

Isoprene emissions from the leaves of velvet bean (Mucuna pruriens L. var utilis) plants exhibited temperature response patterns that were dependent on the plant's growth temperature. Plants grown in a warm regimen (34/28 degrees C, day/night) exhibited a temperature optimum for emissions of 45 degrees C, whereas those grown in a cooler regimen (26/20 degrees C, day/night) exhibited an optimum of 40 degrees C. Several previous studies have provided evidence of a linkage between isoprene emissions and photosynthesis, and more recent studies have demonstrated that isoprene emissions are linked to the activity of isoprene synthase in plant leaves. To further explore this linkage within the context of the temperature dependence of isoprene emissions, we determined the relative temperature dependencies of photosynthetic electron transport, CO(2) assimilation, and isoprene synthase activity. When measured over a broad range of temperatures, the temperature dependence of isoprene emission rate was not closely correlated with either the electron transport rate or the CO(2) assimilation rate. The temperature optima for electron transport rate and CO(2) assimilation rate were 5 to 10 degrees C lower than that for the isoprene emission rate. The dependence of isoprene emissions on photon flux density was also affected by measurement temperature in a pattern independent of those exhibited for electron transport rate and CO(2) assimilation rate. Thus, despite no change in the electron transport rate or CO(2) assimilation rate at 26 and 34 degrees C, the isoprene emission rate changed markedly. The quantum yield of isoprene emissions was stimulated by a temperature increase from 26 to 34 degrees C, whereas the quantum yield for CO(2) assimilation was inhibited. In greenhouse-grown aspen leaves (Populus tremuloides Michaux.), the high temperature threshold for inhibition of isoprene emissions was closely correlated with the high temperature-induced decrease in the in vitro activity of isoprene synthase. When taken together, the results indicate that although there may be a linkage between isoprene emission rate and photosynthesis, the temperature dependence of isoprene emission is not determined solely by the rates of CO(2) assimilation or electron transport. Rather, we propose that regulation is accomplished primarily through the enzyme isoprene synthase.