Oswald T. Avery: Nbel Lureate or noble luminary?

In 1944, Oswald T. Avery and his associates reported that DNA was the chemical substance acting to genetically transform species of pneumococcal bacteria. Many believe that Avery warranted the Nobel Prize for this discovery. Avery's work is evaluated here in light of the Nobel archives, which have made public the names of those who nominated Avery for this award and the basis for each of the nominations. Based on the archival record, it seems that key biological chemists "were not convinced by Avery's claim that DNA was the basis of heredity, that no geneticists nominated Avery, and that most nominators overlooked Avery's work on DNA in favor of his work on the immunogenicity of the bacterial capsule. Three critical scientific factors that adversely affected acceptance of Avery's work were the possibility of protein contamination of DNA, the role of DNA transformation limited to a few species of bacteria, and the possibility that DNA was acting as a chemical mutagen on the true genetic substance. In addition, Avery's own idiosyncratic behavior may have unintentionally confounded acceptance of his groundbreaking discovery.     

In search of the best explanation about the nature of the gene: Avery on pneumococcal transformation

In this paper I present a model of rational belief change, and I show how to use it to obtain a better insight into the debate about the nature of pneumococcal transformation, genes and DNA that took place in the forties, as a result of Oswald T. Avery's work. The model offers a particular elaboration of the concept of inference to the best explanation, along decision theoretic lines. Within this framework, I distinguish different senses in which Avery's team can be said to have proceeded with caution, thus throwing some light upon a persistent source of disagreement among researchers in the history of genetics. In addition, I explain why we are entitled to say that rival parties such as physicist Maclyn McCarty and biochemist Alfred Mirsky were epistemically rational, in spite of the fact that they reached different conclusions on the basis of the same evidence.     

An information-theory model of cellular survival, mutation and transformation and the relevance of this model to chemical carcinogenesis

A model of cellular survival, mutation and transformation is presented in accordance with information theory. A cellular system is considered to be stable with respect to its environment when the vital information the cell expresses at least equals the information requirements of the environment. Environmental agents, such as mutagens, perturb the cell's expression of information such that an imbalance occurs between the cell's information requirement and the cell's ability to express vital information. This imbalance, which is interpreted as the intrinsic entropy of the cell, serves as a measure of biological cell death. If the cell compensates for the altered ability to express information by adapting to a less restricted set of information requirements, then one may view the cell as having undergone a "transformation" to a less restricted phenotype. This paper will elucidate the mathematical inter-relationships of cellular survival, mutation and transformation and will relate these mathematical concepts to chemical carcinogenesis.     

Modelling of syntactical processing in the cortex

Probably the hardest test for a theory of brain function is the explanation of language processing in the human brain, in particular the interplay of syntax and semantics. Clearly such an explanation can only be very speculative, because there are essentially no animal models and it is hard to study detailed neural processing in humans. The approach presented in this paper uses well established basic neural mechanisms in a plausible global network architecture that is formulated essentially in terms of cortical areas and their intracortical and corticocortical interconnections. The neural implementation of this system shows that the comparatively intricate logical task of understanding semantico-syntactical structures can be mastered by a neural network architecture. The system presented also shows additional context awareness, in particular the model is able to correct ambiguous input to a certain degree, e.g. the input "bot show/lift green wall" with an artificial ambiguity between "show" and "lift" is correctly interpreted as "bot show green wall" since a wall is not liftable. Furthermore, the system is able to learn new object words during runtime.     

Transfer of genetic information within a colony of Haemophilus influenzae.

Different Haemophilus cultures were mixed and then spotted onto an agar plate. These mixed colonies were incubated at 37 degrees C and then scored for the presence of recombinants. It was found that conjugative plasmids transferred very efficiently and quickly under these conditions, but only between cells of the same species. Four small plasmids did not transfer at all, nor were they mobilized by the two conjugative plasmids studied. Chromosomal markers transferred very inefficiently. The evidence favored transfer by genetic transformation rather than by conjugation. When mixed cultures were inoculated into broth and then incubated, the transfer of conjugative plasmids was not observed. Transfer of chromosomal markers occurred only when the media used contained Eugonbroth in addition to brain heart infusion, and even then it was very inefficient. The addition of DNase completely eliminated such transfers. This and other evidence indicate that in cell suspensions, chromosomal marker transfer also occurs through transformation. A corrected map of several genetic markers is presented.     

An Infrastructure to Advance the Scholarly Work of Staff Nurses

The traditional role of the acute care staff nurse is changing. The new norm establishes an expectation that staff nurses base their practice on best evidence. When evidence is lacking, nurses are charged with using the research process to generate and disseminate new knowledge. This article describes the critical forces behind the transformation of this role and the organizational mission, culture, and capacity required to support practice that is based on science. The vital role of senior nursing leaders, the nurse researcher, and the nursing research committee within the context of a collaborative governance structure is highlighted. Several well-known, evidence-based practice models are presented. Finally, there is a discussion of the infrastructure created by Yale-New Haven Hospital to advance the scholarly work of the nursing staff.     

Body context and posture affect mental imagery of hands

Different visual stimuli have been shown to recruit different mental imagery strategies. However the role of specific visual stimuli properties related to body context and posture in mental imagery is still under debate. Aiming to dissociate the behavioural correlates of mental processing of visual stimuli characterized by different body context, in the present study we investigated whether the mental rotation of stimuli showing either hands as attached to a body (hands-on-body) or not (hands-only), would be based on different mechanisms. We further examined the effects of postural changes on the mental rotation of both stimuli. Thirty healthy volunteers verbally judged the laterality of rotated hands-only and hands-on-body stimuli presented from the dorsum- or the palm-view, while positioning their hands on their knees (front postural condition) or behind their back (back postural condition). Mental rotation of hands-only, but not of hands-on-body, was modulated by the stimulus view and orientation. Additionally, only the hands-only stimuli were mentally rotated at different speeds according to the postural conditions. This indicates that different stimulus-related mechanisms are recruited in mental rotation by changing the bodily context in which a particular body part is presented. The present data suggest that, with respect to hands-only, mental rotation of hands-on-body is less dependent on biomechanical constraints and proprioceptive input. We interpret our results as evidence for preferential processing of visual- rather than kinesthetic-based mechanisms during mental transformation of hands-on-body and hands-only, respectively.     

Fashioning Racial Selves: Reflexive Practices in the Society for Racial Hygiene

The paper examines the admissions practices of the German Society for Racial Hygiene (Gesellschaft für Rassenhygiene) between 1905 and 1916. It assesses the Society’s changing statutes and the various charts (genealogical, anthropological, and clinical) used to vet prospective members. The Society’s admissions procedures were dual-use technologies, at once serving as evidence for both the larger goals of racial science research and the narrower aims of social inclusion/exclusion. But these procedures can also be interpreted as reflexive practices by which members fashioned their sense of racial self and cultivated relations to that self. Finally, the article situates these practices in the context of histories of human experimentation, the self, and biopolitics.     

Structural and kinetic studies on the solubilization of lecithin by sodium deoxycholate.

Mixed dispersions of egg phosphatidylcholine (PC) and the bile salt sodium deoxycholate (DOC) were prepared by various methods, and their turbidities and proton magnetic resonance spectra were studied as a function of time. The spectra of dispersions prepared by dissolving both components in a common organic solvent and replacing the organic solvent by water did not change with time, indicating that the mixed aggregates formed represent "a state of equilibrium". In the 1H NMR spectra of these mixed aggregates, only signals from small mixed micellar structures were narrow enough to be observed. The dependence of the NMR line widths on the molar ratio of DOC to PC (R) is interpreted in terms of a model for the PC--DOC mixed micelles, according to which PC is arranged as a curved bilayer, the curvature of which increases with increasing R. Upon mixing PC with aqueous solutions of DOC, we found that the mixed aggregates formed are slowly reorganized and ultimately reach the same state of equilibrium. This reorganization was found to be a pseudo-first-order process, the rate constant of which depends linearly upon the detergent concentration. This process involves saturation of the outer bilayers of the multilamellar PC by detergent, followed by transformation of these bilayers into mixed micelles. It is concluded that the solubilization occurs through consecutive "peeling off" of lecithin bilayers.     

Dietary differentiation and the evolution of population genetic structure in a highly mobile carnivore

Recent studies on highly mobile carnivores revealed cryptic population genetic structures correlated to transitions in habitat types and prey species composition. This led to the hypothesis that natal-habitat-biased dispersal may be responsible for generating population genetic structure. However, direct evidence for the concordant ecological and genetic differentiation between populations of highly mobile mammals is rare. To address this we analyzed stable isotope profiles (δ(13)C and δ(15)N values) for Eastern European wolves (Canis lupus) as a quantifiable proxy measure of diet for individuals that had been genotyped in an earlier study (showing cryptic genetic structure), to provide a quantitative assessment of the relationship between individual foraging behavior and genotype. We found a significant correlation between genetic distances and dietary differentiation (explaining 46% of the variation) in both the marginal test and crucially, when geographic distance was accounted for as a co-variable. These results, interpreted in the context of other possible mechanisms such as allopatry and isolation by distance, reinforce earlier studies suggesting that diet and associated habitat choice are influencing the structuring of populations in highly mobile carnivores.     

Immortalized cells and one oncogene in malignant transformation: old insights on new explanation

Background

Nearly thirty years ago, it was first shown that malignant transformation with single oncogene necessarily requires the immortal state of the cell. From that time this thesis for the cells of human origin was not disproved. The basic point which we want to focus on by this short communication is the correct interpretation of the results obtained on the widely used human embryonic kidney 293 (HEK293) cells.

Results

Intensive literature analysis revealed an increasing number of recent studies discovering new oncogenes with non-overlapping functions. Since the 1970s, dozens of oncogenes have been identified in human cancer. Cultured cell lines are often used as model systems in these experiments. In some investigations the results obtained on such cells are interpreted by the authors as a malignant transformation of normal animal or even normal human cells (as for example with HEK293 cells). However, when a cell line gains the ability to undergo continuous cell division, the cells are not normal any more, they are immortalized cells. Nevertheless, the authors consider these cells as normal human ones, what is basically incorrect. Moreover, it was early demonstrated that the widely used human embryonic kidney 293 (HEK293) cells have a relationship to neurons.

Conclusions

Thus, the experiments with established cell lines reinforce the notion that immortality is an essential requirement for malignant transformation that cooperates with other oncogenic changes to program the neoplastic state and substances under such investigation should be interpreted as factors which do not malignantly transform normal cells alone, but possess the ability to enhance the tumorigenic potential of already immortalized cells.     

Laying eyes on headlights: eye movements suggest facial features in cars

Humans' proneness to see faces even in inanimate structures such as cars has long been noticed, yet empirical evidence is scarce. To examine this tendency of anthropomorphism, participants were asked to compare specific features (such as the eyes) of a face and a car front presented next to each other. Eye movement patterns indicated on which visual information participants relied to solve the task and clearly revealed the perception of facial features in cars, such as headlights as eyes or grille as nose. Most importantly, a predominance of headlights was found in attracting and guiding people's gaze irrespective of the feature they were asked to compare--equivalent to the role of the eyes during face perception. This response to abstract configurations is interpreted as an adaptive bias of the respective inherent mechanism for face perception and is evolutionarily reasonable with regard to a "better safe than sorry" strategy.     

Evidence of genocide 7000 BP--Neolithic paradigm and geo-climatic reality

The early Neolithic fortified settlement of Schletz, Lower Austria is emerging as one of the most interesting sites of Linear Pottery culture excavation in Austria. In the course of systematic investigations carried out since 1983, a plethora of unexpected results have been obtained. Specifically, the human skeletal remains of 67 individuals have been found at the base of an oval trench system. Without exception, these remains are characterized by multiple traumatic lesions as well as carnivore gnaw marks. Demographic analysis presents the picture of the entire population of this early farming settlement having been extinguished. Further, the findings suggest that a genocide scenario may have been responsible for the final demise of this settlement. The age and sex distribution reveals a lack of young females, who are interpreted as having been abducted by aggressors. There is however no direct skeletal evidence of aggressors at the site; in fact, the uniformity of Strontium isotope ratios (HR-ICP-MS analysis) implies that all 67 individuals, who were left unburied for months, were indigenous. Supporting evidence of increased levels of inter-human aggression--possibly caused by a broad wave of migration--comes from other contemporary end linear pottery sites in Germany. Such findings are here discussed in the context of a dramatic geological event in the region of the Black Sea shelf at this time (7.550 BP), which led to the submergence of some 100.000 square kilometers of fertile land, and which might have been responsible for subsequent gradual population movements into the interior of Europe.     

Innovative social behavior in chimpanzees (Pan troglodytes)

We present evidence of agonistic buffering in captive chimpanzees, recorded from 1993 until 2005, mainly from ad libitum sampling in over 2000 hr of observation. A total of 33 agonistic buffering episodes were analyzed for context and effects of this complex social behavior. Agonistic buffering was directed at the whole chimpanzee colony as they supported an individual who initially received aggression from the alpha male, independently of the victim's age, sex or social rank. Chimpanzee agonistic buffering behavior is compared with that in other nonhuman primate species, and we describe some particularities of chimpanzee agonistic buffering: the status of the buffers used-socially important offspring such as those from the alpha female-and the social rank of the adult male responsible for the buffering episode-alpha male. Possible functions for this behavior in chimpanzees are suggested as appeasement of group members in a particularly crowded captive setting, and/or as a "forced reconciliation" mechanism. Chimpanzees exhibit behavioral flexibility by adapting themselves to new social and physical situations and use novel behavior to achieve social benefits.     

Brief review of the stylophoran debate

The "calcichordate" theory interprets an extinct group of calcite-plated invertebrates, the stylophorans, as chordates. In this theory, cornute stylophorans are interpreted as stem chordates, whereas mitrate stylophorans are primitive members of the acraniates, tunicates, and craniates. However, this theory discounts major synapomorphies between cornutes and mitrates. These groups constitute a natural, monophyletic group which is here argued to lie within the echinoderm radiation. The "calcichordate" theory is, therefore, rejected because it relies on assumption-driven hypotheses of character transformation which are supported by ambiguous, poor, or missing fossil evidence. Stylophorans may lie at the base of the echinoderm clade and primitively lack pentameral symmetry, therefore casting light on the near-ancestral body organization of the phylum.     

Dopamine, affordance and active inference

The role of dopamine in behaviour and decision-making is often cast in terms of reinforcement learning and optimal decision theory. Here, we present an alternative view that frames the physiology of dopamine in terms of Bayes-optimal behaviour. In this account, dopamine controls the precision or salience of (external or internal) cues that engender action. In other words, dopamine balances bottom-up sensory information and top-down prior beliefs when making hierarchical inferences (predictions) about cues that have affordance. In this paper, we focus on the consequences of changing tonic levels of dopamine firing using simulations of cued sequential movements. Crucially, the predictions driving movements are based upon a hierarchical generative model that infers the context in which movements are made. This means that we can confuse agents by changing the context (order) in which cues are presented. These simulations provide a (Bayes-optimal) model of contextual uncertainty and set switching that can be quantified in terms of behavioural and electrophysiological responses. Furthermore, one can simulate dopaminergic lesions (by changing the precision of prediction errors) to produce pathological behaviours that are reminiscent of those seen in neurological disorders such as Parkinson's disease. We use these simulations to demonstrate how a single functional role for dopamine at the synaptic level can manifest in different ways at the behavioural level.     

Risk calculations for hereditary effects of ionizing radiation in humans

Summary A prediction of the extent to which an additional dose of ionizing radiation increases the natural germ cell mutation rate, and how much such an increase will affect the health status of future human populations is part of the service that human geneticists are expected to offer to human society. However, more detailed scrutiny of the difficulties involved reveals an extremely complex set of problems. A large number of questions arises before such a prediction can be given with confidence; many such questions cannot be answered at our present state of knowledge. However, such predictions have recently been attempted. The 1988 report of the United Nations Scientific Committee for the Effects of Atomic Radiation and the fifth report of the Committee on Biological Effects of Ionizing Radiation of the US National Research Council have presented a discussion of the human genetics problems involved. Empirical data from studies on children of highly radiation-exposed parents, e.g. parents exposed to the atomic bombs of Hiroshima and Nagasaki, or parents belonging to populations living on soil with high background radiation, have been mentioned in this context. Whereas precise predictions are impossible as yet because of deficiencies in our knowledge of medical genetics at various levels, the bulk of the existing evidence points to only small effects of low or moderate radiation doses, effects that will probably be buried in the background noise of changing patterns of human morbidity and mortality.     

The problem of using correlation methods in brain function]

In a series of publications, the author used the correlation hypothesis to explain the main mechanisms of functioning of bat and dolphin echo locators. A good fit of calculated parameters to experimental data was shown. In this work, by the example of generalization of the recognition problem, the use by the brain of correlation methods for solving more general problems independently on the modality of sensor signals was analyzed. In favor of the hypothesis that correlation methods are widely used in brain functioning are the data presented in the paper, which prove that an associative neuron is a suitable analog computer. It is suited for rapid "computation" of the intercorrelation function of discrete input and reference signals. The set of weighting coefficients of neuron synaptic inputs serve as such signals. The pool of associative neurons determines the values on the correlation function in the required range by changing the "numbers" of inputs from neuron to neuron at which discrete signals arrive.