“Virtues” of apartheid

The traditional clinical method, which has served medicine well for over 100 years, had its origins in the integration of physical examination with morbid anatomy in early 19th-century France. Now this method is showing signs of failing to meet some contemporary needs. In particular, there is no means for understanding the inner experience of patients. Previous models of a transformed method have not grappled with the problem of validation. Data on the inner experience of patients are not open to empiric validation in the same way as clinical data. The process of understanding the meaning of an illness is not, therefore, scientific in the conventional sense. There are, none the less, rigorous methods for validating the results of this form of inquiry, notably those of phenomenology. A transformed method should aim to understand the meaning of an illness for the patient as well as provide a clinical diagnosis. The transformation will require a change in the epistemology of medicine and an educational process that encourages reflection and growth of self-knowledge.     

“One-Pot” Syntheses of Malondialdehyde Adducts of Nucleosides

Short, “one-pot” syntheses of malondialdehyde adducts of deoxyguanosine, deoxyadenosine, and deoxycytidine are described. These syntheses proceed in improved yield and easier purification than previous syntheses and are well suited for the preparation of isotopically labeled nucleoside adducts for biomarker and metabolic studies.     

“Facilitation” and “Reversal of Response” of Neurones in the Cerebral Cortex

IN the course of experiments in which movements were elicited by direct electrical stimulation of the cerebral cortex, Graham-Brown^1–4 and Sherrington⁵ found that, after each train of stimuli, there were prolonged changes in the excitability of the cortex. They showed that the motor responses of forelimb muscles in primates, even though elicited by identical cortical stimuli, could be extremely variable. Two of the phenomena they described in detail (see also Lilly⁶) were “facilitation” (the increased motor response resulting from a second train of stimuli when it was applied within 20 s after the first train) and “reversal of response” (when repeated, identical stimulation of the same cortical point elicited flexion instead of extension, or vice versa).     

Coleridge's “Theory of Life”

Coleridge has been seen by some not so much as a poet spoiled by philosophy, but as a philosopher who was also a poet. It could be argued that his major endeavor was an attempt to save the life sciences form the mechanistic interpretation which he saw as the outcome of Lockean “mechanico-corpuscularian” philosophy. This contribution describes that endeavour. It shows its connection to the social circumstances of the time. It discussess its relationship to the poetic sensibility of the “Lake poets” and to the German thought which Coleridge absorbed during and after his sojourn in Gottingen in 1798--99. It describes the nature of his “Theory of Life” as seen not only from the posthumous publication itself, but also from the numerous hints and struggles recorded in his voluminous notebooks, letters and lecture notes. It is concluded that, although never adequately assembled, it forms the only serious attempt to construct a profound alternative to the ultimately mechanistic biology of Charles Darwin and the physiologists of the second half of the century. As such it strongly influenced the young Richard Owen and, as is well known, was eventually overwhelmed by the Darwin-Huxley synthesis of the 1860s. Nevertheless, insofar as Coleridge's concept of life ultimately derived from his ambition to find a way of healing the Cartesian divide, we may wonder whether the recent upsurge in consciousness studies may cause us to look again at his panentheistic ideas and, discarding the obsolete and fanciful metaphysics, recast them into a more acceptable form. This revised version was published online in July 2006 with corrections to the Cover Date.     

Flagellation of“Gluconobacter” melanogenus

Summary Electron-micrographs ofGluconobacter melanogenus strain AC 8 (formerlyG. liquefaciens), andG. melanogenus strain U 4, have conclusively confirmed the findings ofShimwell andCarr (1959),Stouthamer (1960), andLeifson (private communication), that these strains are not polarly flagellatedAcetomonas orGluconobacter strains, but peritrichously flagellated acetate-oxidisingAcetobacter ones. When transferred to the latter genus all evidence that these two genera are derived from a “common pool of ancestors”, as claimed byDe Ley (1961), disappears.     

“Maturation” of DNA duplexes

Reassociation of typical single-copy DNAs, like E. coli DNA, even when performed at relatively low temperatures, results in the formation of perfect duplexes with thermal stability very close to that of the native DNA. In contrast, duplexes of mouse repeated DNA as well as duplexes of Streptomyces DNA prepared under the same conditions, show a low thermal stability and undergo post-reassociation changes upon prolonged incubation. These changes, called maturation of the DNA duplexes, result in increasing of their thermal stability. Some of the factors affecting the rate of maturation are studied. The implication of the maturation process in reassociation analysis and in characterization of the heterogeneity of DNA is discussed.     

Dynamics of “neuron ring”

Summary Dynamics of neuron ring has been studied by means of computer simulation. The ring is formed of some number of identical neurons which loop together with lateral inhibitions and are stimulated by a command neuron. In this model, we assumed that each neuron has individual activity intrinsically without any inputs. The function of each neuron is essentially the same as that of Reiss' model; each neuron receives one excitatory and two inhibitory signals and when the membrane potential exceeds the instantaneous values of threshold, the neuron fires and sends out signals. Fatigue effect is also introduced in this model; after firing, the threshold level rises up for a period. This report is mainly concerned with the mechanism by which the individual activities of each neuron transit into an ordered behavior as a whole when they are externally stimulated. Results can be summarized as follows: The individual random activities of neurons can be organized and transfered into an ordered behavior on a completely symmetrical neuron ring if externally stimulated and the following conditions are satisfied; 1. the individual inherent activity is within a moderate range, 2. the fatigue effect is large enough, 3. external stimulation is high enough and 4. neurons in the ring are laterally inhibited. The individual activity and the lateral inhibition are essential to generate a meaningful output pattern as a group and fatigue effect acts as a stabilizing factor of the generated pattern.     

The Teaching of “Adaptation”

The use of the data from various athletic sports for exercises in the interpretation of data is proposed, and accounts are given of two such exercises. The first looks at the relationship between time and distance in world records for men running. When the logarithm of the time is plotted against the logarithm of the distance a straight line is produced. Thefactors that govern the speeds at which various distances are run are discussed and the application of these to other sports and to animals other than man is briefly mentioned. The second exercise looks at anomalous performances by men running in the 1968 Olympic Games which took place at high altitude. It is shown that while the lowered air resistance increased the speeds in sprint events, and the lowered oxygen content slowed down speeds in long distance events, these were not the only factors involved in limiting speeds.

Among the advantages of the use of such data are that they are readily and easily available, that they are the result of a lengthy selection process involving many subjects, that they appeal to students interested in sport and that they can link courses in biology and physical education.     

“Mild” Uncoupling of Mitochondria

Recently, it was proposed that the thyroid hormone-mediated uncoupling in mitochondria is involved in the cellular defence system against free radicals (Skulachev V.P. (1996) Quart. Rev. Biophys. 29:169–202). This phenomenon was named mild uncoupling. It was postulated to be a protein-mediated process controlled by several factors. The data reported during the past 40 years, pointing to the protein-mediated uncoupling mechanism in mitochondria, are reviewed in a context of hypothetical properties of mild uncoupling. The mechanism of mild uncoupling is suggested to be the following: (a) mitochondria possess protein(s) that regulate the proton permeability of inner mitochondrial membrane; (b) these proteins are regulated by binding of an unidentified low-molecular-weight endogenous compound with properties resembling those of the most active artificial uncouplers like FCCP and SF6847; (c) the interaction of this compound with its target protein(s) is modulated by a thyroid hormone in a positive (i.e. enhancing the proton permeability) way and by sex steroid hormones in a negative way; (e) endogenous fatty acids can attenuate the influence of both thyroid and steroid hormones.     

“Neutral theory” and the dynamics of the evolution of “Modern” human morphology

There is a widespread assumption, even among those who reject the Synthetic Theory of Evolution, that the form of “modern”Homo sapiens is somehow superior to that of archaicHomo sapiens (Tattersall 2000). Those who accept the general outlook of evolutionary biology also tend to assume that “modern” form emerged because it was selected for, which also implies that it was better than that which preceded it. However, after years of using craniofacial measurements to compare human populations, I finally came to realize that, with only a few exceptions, the dimensions measured have no relation to differences in adaptation (Brace 1989, 1996, 2000; Brace et al., 1993). Elsewhere the conclusion has been supported that what is shown by craniometrics is selectively neutral on the average (Relethford 2002). With the documentation that approximately 95% of the genome is not functional, molecular genetics has proved to be useful in documenting the length of time of separation of related human populations by investigating the differences that have accumulated in the neutral parts of the genome. Not surprisingly, the picture revealed by the study of genetic differences is very similar to the one revealed by the study of craniometric differences (Brace et al., 2001). For this reason, the logic behind the “neutral theory” in molecular genetics is very similar to that applied to what happens to morphological characteristics when selection ceases (Brace 1963; Kimura 1968). The difference is that random changes in the neutral part of the genome have no other consequences. However, random changes in the genes that produce specific aspects of morphology will be visible even when selection is no longer controlling the particular trait in question. From an assessment of what random changes in genes controlling morphological traits are likely to do, it follows that the most likely change will probably be a reduction in the trait in question, i.e. the Probable Mutation Effect will produce structural reduction. When survival in the temperate zone during the last glaciation dependend on “obligatory cooking”, one of the unintended consequences was a reduction in the selective pressures maintaining a Middle Pleistocene-sized dentition. The result was a gradual reduction in tooth size and a conversion, of a Neanderthal-sized face into one of “modern” dimensions. The manufacture and use of string for snares and nets similarly reduced the selective pressures maintaining post-cranial levels of robustness and muscularity. The reduction in the latter resulted in the emergence of moderm post-cranial robustness out of what had been a Neanderthal level,in situ wherever the technology can be documented and without any need for invasions and replacements.     

The “Normalization” of Intersex Bodies and “Othering” of Intersex Identities in Australia

Once described as hermaphrodites and later as intersex people, individuals born with intersex variations are routinely subject to so-called “normalizing” medical interventions, often in childhood. Opposition to such practices has been met by attempts to discredit critics and reasserted clinical authority over the bodies of women and men with “disorders of sex development.” However, claims of clinical consensus have been selectively constructed and applied and lack evidence. Limited transparency and lack of access to justice have helped to perpetuate forced interventions. At the same time, associated with the diffusion of distinct concepts of sex and gender, intersex has been constructed as a third legal sex classification, accompanied by pious hopes and unwarranted expectations of consequences. The existence of intersex has also been instrumentalized for the benefit of other, intersecting, populations. The creation of gender categories associated with intersex bodies has created profound risks: a paradoxically narrowed and normative gender binary, maintenance of medical authority over the bodies of “disordered” females and males, and claims that transgressions of social roles ascribed to a third gender are deceptive. Claims that medicalization saves intersex people from “othering,” or that legal othering saves intersex people from medicalization, are contradictory and empty rhetoric. In practice, intersex bodies remain “normalized” or eliminated by medicine, while society and the law “others” intersex identities. That is, medicine constructs intersex bodies as either female or male, while law and society construct intersex identities as neither female nor male. Australian attempts at reforms to recognize the rights of intersex people have either failed to adequately comprehend the population affected or lacked implementation. An emerging human rights consensus demands an end to social prejudice, stigma, and forced medical interventions, focusing on the right to bodily integrity and principles of self-determination.     

Synthesis of “Reversed” Methylenecyclopropane Analogues of Antiviral Phosphonates

Synthesis of “reversed” methylenecyclopropane analogues of nucleoside phosphonates 6a,7a, 6b, and 7b is described. 1-Bromo-1-bromomethylcyclopropane 8 was converted to the bromocyclopropyl phosphonate 9 by Michaelis-Arbuzov reaction with triisopropyl phosphite. Base-catalyzed β-elimination and deacetylation gave the key Z- and E-hydroxymethylcyclopropyl phosphonates 10 and 11 separated by chromatography. The Mitsunobu type of alkylation of 10 or 11 with adenine or 2-amino-6-chloropurine afforded phosphonates 12a, 12b, 13a, and 13b. Acid hydrolysis furnished the adenine and guanine analogues 6a, 7a, 6b, and 7b. The E and Z configuration was assigned on the basis of NOE experiments with phosphonates 6b and 7b. All Z- and E-isomers were also distinguished by different chemical shifts of CH₂O or CH₂N (H₄ or H_4′). Significant differences of the chemical shifts of the cyclopropane C_3(3’) carbons and coupling constants ³J_P,C2(2’) or ³J_P,C3(3’) selective for the Z- or E-isomers were also noted. Phosphonates 6a, 7a, 6b, and 7b are devoid of significant antiviral activity.     

A Review of: “Handbook of Material Culture”

The examination of a well‐documented petroglyph site, located near the northeastern shoreline of now‐dry Owens Lake, California, is used as a springboard for a review of explanatory models for the interpretation of rock art sites in California and the Great Basin. Interpretive models and methods of analysis used by Julian Steward, Robert Heizer, and others who have visited or reported on this site are reviewed. The persistence of Heizer's “hunting‐magic” explanation for the creation of the rock art is used as one of several examples of how preconceived notions can affect interpretations of ancient art.     

Synthesis of “Reversed” and “Double Headed” Nucleosides

Abstract

The synthesis of several partially and fully deprotected “reversed” nucleosides are described starting from “reversed” 5-iodouracil-1-yl nucleoside 1. The preparation of a novel purine-purine and mixed purine-pyrimidine “double headed” nucleosides via “reversed” purine nucleoside 12 is also described.     

Nature of plasmalemmal functional “hemichannels”

The molecular identity of the protein forming “hemichannels” at non-junctional membranes is disputed. The family of gap junction proteins, innexins, connexins, and pannexins share several common features, including permeability characteristics and sensitivity to blocking agents. Such overlap in properties renders the identification of which of these protein species actually establishes the non-junctional membrane conductance and permeability quite complicated, especially because in vertebrates pannexins and connexins have largely overlapping distributions in tissues. Recently, attempts to establish criteria to identify events that are “hemichannel” mediated and those to allow the distinction between connexin- from pannexin-mediated events have been proposed.Here, I present an update on that topic and discuss the most recent findings related to the nature of functional “hemichannels” focusing on connexin43 and pannexin1. This article is part of a Special Issue entitled: The Communicating junctions, composition, structure and characteristics.