Siegel,Schaudinn, Fleck and the Etiology of Syphilis

In 1905 two different etiologic agents for syphilis were proposed in Berlin, one, the Cytorrhyctes luis, by John Siegel, the other, Spirochaete pallida, by Fritz Schaudinn. Both scientists were pupils of Franz Eilhard Schulze, and were outsiders to the Berlin medical establishment. Both belonged to the same thought collective, used the same thought style, and started from the same supposition that the etiologic agent of syphilis must be a protist. Both used the same morphological approach, the same microscopes and the same stains. Both presented their findings in the same societies, used the same rhetoric, published in the same journals, used the same arguments to criticise each other's shortcomings. Both were backed by powerful institutions and enlisted the support of prestigious patrons. Within half a year, the scientific community at large had in its overwhelming majority accepted Schaudinn's results and rejected those of Siegel. Social forces thus cannot be shown to have played any role in deciding the issue. Ludwik Fleck's suggestion that ‘appropriate influence’ and a ‘proper measure of publicity throughout the thought collective’ would have been sufficient for Siegel's ideas to win the day is untenable.     

Convergence, adaptation, and constraint

Convergent evolution of similar phenotypic features in similar environmental contexts has long been taken as evidence of adaptation. Nonetheless, recent conceptual and empirical developments in many fields have led to a proliferation of ideas about the relationship between convergence and adaptation. Despite criticism from some systematically minded biologists, I reaffirm that convergence in taxa occupying similar selective environments often is the result of natural selection. However, convergent evolution of a trait in a particular environment can occur for reasons other than selection on that trait in that environment, and species can respond to similar selective pressures by evolving nonconvergent adaptations. For these reasons, studies of convergence should be coupled with other methods-such as direct measurements of selection or investigations of the functional correlates of trait evolution-to test hypotheses of adaptation. The independent acquisition of similar phenotypes by the same genetic or developmental pathway has been suggested as evidence of constraints on adaptation, a view widely repeated as genomic studies have documented phenotypic convergence resulting from change in the same genes, sometimes even by the same mutation. Contrary to some claims, convergence by changes in the same genes is not necessarily evidence of constraint, but rather suggests hypotheses that can test the relative roles of constraint and selection in directing phenotypic evolution.     

Number, unit, and utility in a Mayan community: the relation between use-value, labour-power, and personhood

Rather than asking how two use-values can have the same exchange-value, this article asks how two distinct entities can have the same use-value. Among the Q'eqchi'-Maya, substitution ( eeqaj ) refers to activities as disparate as house-building, civil-religious elections, vengeance, loans, illness cures, adultery, and namesakes. Such practices involve the exchange of one entity for another entity, insofar as these entities have shared properties, and insofar as they hold a role in a necessary position. Substitution is interpreted as social processes whereby substances get utilized, unitized, and numericalized, and this local articulation of use-value is theorized in terms of labour-power and personhood.     

Sleep, emotions, and visceral control

It is known that sleep is connected with sensory isolation of the brain, inactivation of the consciousness and reorganization of the electrical activity in all cerebral cortical areas. On the other hand, sleep deprivation leads to pathology in visceral organs and finally to the death of animals, while there are no obvious changes in the brain itself. It is still unclear how the changes in the brain activity during sleep could be connected with the visceral health. We assumed that the same brain areas and the same neurons that, in wakefulness, process exteroceptive information, switch, during sleep, to the processing of the interoceptive information. Thus, the central nervous system is involved in regulating the life support functions of the body during sleep. The results of our experiments supported this hypothesis, explained many observations obtained in somnology, and offered mechanisms of several pathological states connected with sleep. However, at the present level of the visceral sleep theory, there is no understanding of the well-known link between the emotional reactions of the body and transition from wakefulness to sleep, and sleep quality. In this study, an attempt is undertaken to combine the visceral theory of sleep with the need-informational theory of emotions proposed by P. Simonov. The visceral theory of sleep assumes that in living organisms there is a constant monitoring of the correspondence of the visceral parameters to the genetically determined values. Mismatch signals evoke the feeling of tiredness and the need of sleep. This sleep need enters the competition with other actual needs of the body. In accordance with the theory of Simonov, emotions connected with a particular need play an important role in their ranking for satisfaction. We propose that emotional estimation of the sleep need based on visceral signals occurs in the same brain structures which undertake this estimation for other behavioral needs in wakefulness. During sleep, the same brain structures involved in estimating emotions continue to rank visceral needs and define their order for processing in the cortical areas and in the highest centers of visceral integration. In the context of the proposed hypothesis, we discuss the results of the studies on the link between sleep and emotions.     

The radiosensitivities of lymphocytes from pig,sheep, goat and cow

Dose-effect curves for X-irradiation in vitro were determined on cultured blood lymphocytes of four mammalian speciec — cow, goat, sheep and pig — having approximately the same number of chromosome arms, the same nuclear volume and the same DNA content. The data from cow, but not those from the other species, exhibited significant inhomogeneity between the experiments. On inspection the numerical yields appear not to differ greatly in the lower dose range. Evaluation of the parameters according to the quadratic law and the power law, however, demonstrate significant differences. Pig differs from the other species regardless of which presentation is chosen. For the power law a significant difference is also found between goat and sheep.     

Carotenoid composition, concentrations, and relationships in various human organs

The carotenoid content of 10 different organs obtained at autopsy from 16 humans was determined using a high-performance liquid chromatography assay. The same qualitative pattern of carotenoids found in serum was found for all the tissues, although there were important quantitative differences in the different carotenoids between organs. The median levels of zeaxanthins, lycopene and beta-carotene varied disproportionately between organs; similar levels of one carotenoid for two organs would not predict similar levels of another carotenoid for the same organs. Similarly, there was not a consistent relationship between all the carotenoids for a given organ. The uneven but wide tissue distribution of most dietary carotenoids may indicate an active biological role for these compounds.     

Carcinoembryonic antigen, ferritin, tissue polypeptide antigen, and CA15/3 in breast cancer: relationship between carcinoma and normal breast tissue

The study of tumor markers in breast cancer tissue may supply information on the tumor's biological features and its clinical behaviour. Forty-nine primary breast cancer patients are evaluable to date. CEA, ferritin, TPA and CA15/3 were measured with radioimmunometric methods in the cytosol of carcinoma and normal tissue from the same breast. The concentrations of the four markers were higher in the tumor than in normal tissue in 42/49 cases for CEA, 47/49 for ferritin, 42/49 for TPA and in 24/29 for CA15/3. However, an overlap was found between carcinoma and normal tissue levels, particularly for CEA and TPA. We can conclude that the four substances studied may be markers of malignancy in breast carcinoma when non-malignant breast tissue from the same patient is determined at the same time, whereas assays within a single, unknown breast tissue sample may be useful only in the case of ferritin and, partly, CA15/3.     

A Single Radioimmunological Assay for Serotonin, N-Acetylserotonin, 5-Methoxytryptamine, and Melatonin

Abstract: A radioimmunoassay of melatonin using a new iodinated derivative has been developed. Simple chemical treatments have then been designed to convert serotonin, N-acetylserotonin, and 5-methoxytryptamine to melatonin. Thus these four molecules, belonging to the same metabolic pathway, were separately assayed in the same radioimmunological system at the same sensitivity level (0.01 pmol). Some biological results on the circadian variations of melatonin and serotonin in blood, pineal, and miscellaneous brain structures are presented.     

3D domain swapping, protein oligomerization, and amyloid formation

In 3D domain swapping, first described by Eisenberg, a structural element of a monomeric protein is replaced by the same element from another subunit. This process requires partial unfolding of the closed monomers that is then followed by adhesion and reconstruction of the original fold but from elements contributed by different subunits. If the interactions are reciprocal, a closed-ended dimer will be formed, but the same phenomenon has been suggested as a mechanism for the formation of open-ended polymers as well, such as those believed to exist in amyloid fibrils. There has been a rapid progress in the study of 3D domain swapping. Oligomers higher than dimers have been found, the monomer-dimer equilibrium could be controlled by mutations in the hinge element of the chain, a single protein has been shown to form more than one domain-swapped structure, and recently, the possibility of simultaneous exchange of two structural domains by a single molecule has been demonstrated. This last discovery has an important bearing on the possibility that 3D domain swapping might be indeed an amyloidogenic mechanism. Along the same lines is the discovery that a protein of proven amyloidogenic properties, human cystatin C, is capable of 3D domain swapping that leads to oligomerization. The structure of domain-swapped human cystatin C dimers explains why a naturally occurring mutant of this protein has a much higher propensity for aggregation, and also suggests how this same mechanism of 3D domain swapping could lead to an open-ended polymer that would be consistent with the cross-beta structure, which is believed to be at the heart of the molecular architecture of amyloid fibrils.     

Immunocytochemical localization of prorenin, renin, and cathepsins B, H, and L in juxtaglomerular cells of rat kidney

To examine the correlation of localization of prorenin, renin, and cathepsins B, H, and L, immunocytochemistry was applied to rat renal tissue, using a sequence-specific anti-body (anti-prorenin) that recognizes the COOH terminus of the rat renin prosegment. In serial semi-thin sections, immunodeposits for prorenin, renin, and cathepsins B, H, and L were localized in the same juxtaglomerular (JG) cells. Immunodeposits for renin were detected throughout the cytoplasm of the cells, whereas those for prorenin were detected in the perinuclear region. Immunoreactivity for cathepsin B was stronger than that for cathepsins H and L. By electron microscopy, prorenin was localized in small (immature) granules but not in large mature granules, whereas renin was localized mainly in mature granules. In serial thin sections, prorenin, renin, and cathepsin B were colocalized in the same immature granules containing heterogeneously dense material (intermediate granules). By double immunostaining, co-localization of renin with cathepsins B, H, or L was demonstrated in mature granules. The results suggest the possibility that processing of prorenin to renin occurs in immature granules of rat JG cells, and cathepsin B detected in JG cells may be a major candidate for the maturation of renin.     

Super folds,networks, and barriers

Exhaustive enumeration of sequences and folds is conducted for a simple lattice model of conformations, sequences, and energies. Examination of all foldable sequences and their nearest connected neighbors (sequences that differ by no more than a point mutation) illustrates the following: (i) There exist unusually large number of sequences that fold into a few structures (super‐folds). The same observation was made experimentally and computationally using stochastic sampling and exhaustive enumeration of related models. (ii) There exist only a few large networks of connected sequences that are not restricted to one fold. These networks cover a significant fraction of fold spaces (super‐networks). (iii) There exist barriers in sequence space that prevent foldable sequences of the same structure to “connect” through a series of single point mutations (super‐barrier), even in the presence of the sequence connection between folds. While there is ample experimental evidence for the existence of super‐folds, evidence for a super‐network is just starting to emerge. The prediction of a sequence barrier is an intriguing characteristic of sequence space, suggesting that the overall sequence space may be disconnected. The implications and limitations of these observations for evolution of protein structures are discussed. Proteins 2012. © 2011 Wiley Periodicals, Inc.     

Carcinogenesis, cancer therapy and chemoprevention

Carcinogenesis and cancer therapy are two sides of the same coin, such that the same cytotoxic agent can cause cancer and be used to treat cancer. This review links carcinogenesis, chemoprevention and cancer therapy in one process driven by cytotoxic agents (carcinoagents) that select either for or against cells with oncogenic alterations. By unifying therapy and cancer promotion and by distinguishing nononcogenic and oncogenic mechanisms of resistance, I discuss anticancer- and chemopreventive agent-induced carcinogenesis and tumor progression and, vice versa, carcinogens as anticancer drugs, anticancer drugs as chemopreventive agents and exploiting oncogene-addiction and drug resistance for chemoprevention and cancer therapy.     

Cultural variations in the placebo effect: ulcers, anxiety, and blood pressure

An analysis of the control groups in double-blind trials of medicines demonstrates broad variation--from 0 to 100 percent--in placebo effectiveness rates for the same treatment for the same condition. In two cases considered here, drug healing rates covary with placebo healing rates; placebo healing is the ultimate and inescapable "complementary medicine." Several factors can account for the dramatic variation in placebo healing rates, including cultural ones. But because variation differs by illness, large placebo effects for one condition do not necessarily anticipate large placebo effects for other conditions as well. Deeper understanding of the intimate relationship between cultural and biological processes will require close ethnographic scrutiny of the meaningfulness of medical treatment in different societies.     

Intestinal microecology of the adult population of Mongolia, Switzerland, and Russia

The study of intestinal microflora was made in clinically healthy young adults living in rural areas of Mongolia, in Russia (Moscow) and in Switzerland, as well as in Swiss citizens of elderly age groups (55-68 and 87-94 years). Essential differences in the quantitative and qualitative characteristics of intestinal microflora both in the inhabitants of different countries as well as in people belonging to different age groups in the same country were established. The results of the study demonstrated the expediency of working out the criteria of the norm for intestinal microflora both for the population of different countries and for people living in the same country, but belonging to different age groups.     

CD1a-, b-, and c-restricted TCRs recognize both self and foreign antigens

Individual CD1-restricted T cells can recognize either endogenous or foreign lipid Ags, but the extent to which the same CD1-restricted TCR can react to both self and microbial lipids is unknown. In this study, we have identified CD1a-, CD1b-, and CD1c-restricted T cells from normal human donors that induce cytolysis and secrete copious IFN-gamma in response to self-CD1 expressed on monocyte-derived dendritic cells. Remarkably, microbial Ags presented by CD1 are even more potent agonists for these same T cells. The alphabeta T cell receptors from such clones are diverse and confer specificity for both self-CD1 and foreign lipid Ags. The dual reactivity of these CD1-restricted cells suggests that the capacity for rapid responses to inflammatory stimuli without memory coexists with the capacity for strong Ag-specific responses and the generation of memory in vivo.     

Synthesis,characterization, cytotoxic activity,and cellular accumulation of dinuclear platinum complexes derived from N,N'-di-(2-aminoethyl)-1,3-diamino-2-propanol,aryl substituted N-benzyl-1,4-butanediamines,and N-benzyl-1,6-hexanediamines

This work describes the synthesis and characterization of six new dinuclear platinum complexes having N,N'-di-(2-aminoethyl)-1,3-diamino-2-propanol, aryl substituted N-benzyl-1,4-butanediamines and N-benzyl-1,6-hexanediamines as ligands. They were prepared by the reaction of cis-[PtCl(2)(DMSO)(2)] (DMSO=dimethyl sulfoxide) with the appropriate ligand in water, except for one of them, which was prepared from K(2)PtCl(4). We also report the cytotoxic activity and cellular accumulation of three of these complexes in a human small-cell lung carcinoma cell line and its resistant subline. Resistant cells exhibited a lesser degree of cross-resistance to these compounds when compared to cisplatin. The accumulation of platinum in both cell lines followed the same pattern, i.e. approximately the same intracellular platinum concentration yielded the same cytotoxic effect independent of the nature of the platinum complex used.     

Hydroxytyrosol and tyrosol esters partitioning into,location within,and effect on DOPC liposome bilayer behavior

The phenols hydroxytyrosol and tyrosol made abundantly available through olive oil processing were enzymatically transesterified into effective lipophilic antioxidants with cuphea oil. The hydroxytyrosyl and tyrosyl esters made from cuphea oil were assessed for their ability to partition into, locate within and effect the bilayer behavior of 1,2-dioloeoylphosphatidylcholine liposomes and compared to their counterparts made from decanoic acid. Partitioning into liposomes was on the same scale for both hydroxytyrosyl derivatives and both tyrosyl derivatives. All were found to locate nearly at the same depth within the bilayer. Each was found to affect bilayer behavior in a distinct manner.     

Normothermy,torpor, and arousal in hedgehogs (Erinaceus europaeus) from Dunedin

Abstract

We measured oxygen consumption of hedgehogs from Dunedin during normothermy, torpor, and arousal from torpor during the winter. Basal oxygen consumption and minimum thermal conductance were not significantly different from expected values for an average mammal of the same body mass. Torpid oxygen consumption at 5°C was only 0.5% of resting normothermic oxygen consumption at the same temperature. Oxygen consumption during arousal was not significantly different to that predicted theoretically or to that recorded during resting normothermy over the same time period. Using previous measures of pre‐hibernal body fat content, we build a simple model showing the relative energetic implications for a hedgehog of entering or not entering hibernation, and suggest that, at low temperatures, body fat stores would be depleted in <1 day and >100 days in non‐hibernating and hibernating hedgehogs, respectively.     

Comparison of fresh, ethanol-preserved, and paraffin-embedded samples in DNA flow cytometry

Fresh, ethanol-preserved, and formalin-fixed and paraffin-embedded samples taken from the same part of 15 human tumors, and from one normal spleen and one pancreas were analyzed for nuclear DNA content by flow cytometry. The coefficient of variation (CV) values of the G1 peaks were smaller in the fresh than in the other samples (P less than 0.001). The DNA ploidy of the tumors was the same in all types of samples. The DNA indices (DIs) measured from either ethanol-preserved or formalin-fixed tissue correlated strongly with those obtained from fresh tissue (P less than 0.001), although they tended to be somewhat smaller in the fresh samples. The S-phase fractions measured from all types of samples were of the same order of magnitude in most cases (P less than 0.001). Uninterpretable histograms were most often obtained from fresh samples. Identical DI values and rather constant S-phase fractions were obtained from ethanol-preserved samples stored at 4 degrees C for up to 5 months. It is concluded that all three types of samples are suitable for the determination of DNA ploidy, DI, and S-phase fraction and that 50% ethanol is suitable for long-term preservation of flow cytometric samples.