Maladaptive "gambling" by pigeons

When humans buy a lottery ticket or gamble at a casino they are engaging in an activity that on average leads to a loss of money. Although animals are purported to engage in optimal foraging behavior, similar sub-optimal behavior can be found in pigeons. They show a preference for an alternative that is associated with a low probability of reinforcement (e.g., one that is followed by a red hue on 20% of the trials and then reinforcement or by a green hue on 80% of the trials and then the absence of reinforcement) over an alternative that is associated with a higher probability of reinforcement (e.g., blue or yellow each of which is followed by reinforcement 50% of the time). This effect appears to result from the strong conditioned reinforcement associated with the stimulus that is always followed by reinforcement. Surprisingly, although it is experienced four times as much, the stimulus that is never followed by reinforcement does not appear to result in significant conditioned inhibition (perhaps due to the absence of observing behavior). Similarly, human gamblers tend to overvalue wins and undervalue losses. Thus, this animal model may provide a useful analog to human gambling behavior, one that is free from the influence of human culture, language, social reinforcement, and other experiential biases that may influence human gambling behavior.     

Comments on "The Grand Objectives" by Thomas E. Graedel

In "The Grand Objectives: A Framework for Prioritized Grouping of Environmental Concerns in Life-Cycle Assessment". Thomas Graedel (1997) proposed an elegant schema for prioritizing environmental concerns. It operates at three levels: grand objectives, environmental concerns, and targeted activities. I argue that consensus is most likely on the first and third levels, but that the middle level, environmental concerns, is more problematic. Even among individuals who agree on general societal directions, strong differences of views can occur regarding specific technologies. I illustrate by applying Graedel's system to his "radionuclide" category, under his first grand objective (human species extinction). I use the example of nuclear waste to illustrate how values are inextricably involved at the "environmental concerns" level. My analysis suggests ways to enhance the utility of Graedel's useful system.     

The jury is out on "guilt by association" trials.

The availability of comprehensive protein-protein interaction maps will significantly enhance medical research and aid the functional characterisation of novel genes. To date, the largest scale studies of protein-protein interactions have used the yeast two hybrid method. In this review we take a closer look at the different approaches used in these studies and discuss some key considerations that should be taken into account when designing high throughput interaction mapping projects.     

The impact of multifunctional genes on "guilt by association" analysis

Many previous studies have shown that by using variants of "guilt-by-association", gene function predictions can be made with very high statistical confidence. In these studies, it is assumed that the "associations" in the data (e.g., protein interaction partners) of a gene are necessary in establishing "guilt". In this paper we show that multifunctionality, rather than association, is a primary driver of gene function prediction. We first show that knowledge of the degree of multifunctionality alone can produce astonishingly strong performance when used as a predictor of gene function. We then demonstrate how multifunctionality is encoded in gene interaction data (such as protein interactions and coexpression networks) and how this can feed forward into gene function prediction algorithms. We find that high-quality gene function predictions can be made using data that possesses no information on which gene interacts with which. By examining a wide range of networks from mouse, human and yeast, as well as multiple prediction methods and evaluation metrics, we provide evidence that this problem is pervasive and does not reflect the failings of any particular algorithm or data type. We propose computational controls that can be used to provide more meaningful control when estimating gene function prediction performance. We suggest that this source of bias due to multifunctionality is important to control for, with widespread implications for the interpretation of genomics studies.     

"Hit-and-run" transformation by adenovirus oncogenes

According to classical concepts of viral oncogenesis, the persistence of virus-specific oncogenes is required to maintain the transformed cellular phenotype. In contrast, the "hit-and-run" hypothesis claims that viruses can mediate cellular transformation through an initial "hit," while maintenance of the transformed state is compatible with the loss ("run") of viral molecules. It is well established that the adenovirus E1A and E1B gene products can cooperatively transform primary human and rodent cells to a tumorigenic phenotype and that these cells permanently express the viral oncogenes. Additionally, recent studies have shown that the adenovirus E4 region encodes two novel oncoproteins, the products of E4orf6 and E4orf3, which cooperate with the viral E1A proteins to transform primary rat cells in an E1B-like fashion. Unexpectedly, however, cells transformed by E1A and either E4orf6 or E4orf3 fail to express the viral E4 gene products, and only a subset contain E1A proteins. In fact, the majority of these cells lack E4- and E1A-specific DNA sequences, indicating that transformation occurred through a hit-and-run mechanism. We provide evidence that the unusual transforming activities of the adenoviral oncoproteins may be due to their mutagenic potential. Our results strongly support the possibility that even tumors that lack any detectable virus-specific molecules can be of viral origin, which could have a significant impact on the use of adenoviral vectors for gene therapy.     

Laboratory investigations on "postvaccinall rabies" caused by live sheep-brain vaccine.

The viral ethiology of postvaccinal complications among 30 dogs vaccinated by live antirabies vaccine (Umeno-Doi type, sheep brain vaccine) was fully confirmed. Three lots of virulent vaccine were inoculated subcutaneously into groups of "Wistar" rats according to the different schemes. Between the 1st and 12th day after the end of the vaccination there were no isolations of fixed virus in direct and blind i.c. passages of suspensions made from the thalamus area on succkling mice and rats. Also the viral antigen in the CNS of vaccinated but apparently healthy rats was undetectable. The "postvaccinal rabies" with the next isolation of fixed r.v. in the CNS was developed experimentally in rats only following the subcutaneous injection of the crude sheep-brain's and spinal cord's suspensions--composing the materials to production of antirabies vaccine.     

Dimer formation by a "monomeric" protein

Dimeric proteins can arise by the swapping of structural domains between monomers. The prevalence of this occurrence is unknown. Ribonuclease A (RNase A) is assumed to be a monomer near physiological conditions. Here, this hypothesis is tested and found to be imprecise. The two histidine residues (His12 and His119) in the active site of RNase A arise from two domains (S-peptide and S-protein) of the protein. The H12A and H119A variants have 10(5)-fold less ribonucleolytic activity than does the wild-type enzyme. Incubating a 1:1 mixture of the H12A and H119A variants at pH 6.5 and 65 degrees C results in a 10(3)-fold increase in ribonucleolytic activity. A large quantity of active dimer can be produced by lyophilizing a 1:1 mixture of the H12A and H119A variants from acetic acid. At pH 6.5 and 65 degrees C, the ribonucleolytic activity of this dimer converges to that of the dimer formed by simply incubating the monomers, as expected for a monomer-dimer equilibrium. The equilibrium dissociation constant for the dimer is near 2 mM at both 65 and 37 degrees C. This value of Kd is only 20-fold greater than the concentration of RNase A in the cow pancreas, suggesting that RNase A dimers exist in vivo. The intrinsic ability of RNase A to form dimers under physiological conditions is consistent with a detailed model for the evolution of homodimeric proteins. Dimers of "monomeric" proteins could be more prevalent than is usually appreciated.     

Commentary on: "Photosynthesis and negative entropy production" by Jennings and coworkers

This commentary argues against the view that photochemical energy conversion violates the second law of thermodynamics, as expressed in a recent paper [R.C. Jennings, E. Engelmann, F. Garlaschi, A.P. Casazza, G. Zucchelli. Photosynthesis and negative entropy production. Biochim. Biophys. Acta 1709 (2005) 251-255]. The basic principles of free energy conversion by a photo-electrochemical cell are outlined, emphasizing the fact that the potential depends on the relative population of the excited state and thus on the illumination intensity.     

Bud formation by the yeast Saccharomyces cerevisiae is directly dependent on "start"

Cells of the yeast Saccharomyces cerevisiae, which bear a cdc4 gene mutation, arrest early in the cell cycle but continue to produce buds in a periodic fashion. We show here that this periodic bud formation by cells already arrested at the CDC4 step is inhibited if the cell cycle regulatory step "start" is also specifically blocked by mutation or by the presence of the yeast mating pheromone alpha-factor. Thus, the characteristic periodic bud formation by cdc4 mutant cells requires the continued ability to perform start. This finding raises questions concerning the nature of start; these issues are discussed.     

Fractionation of "tricholysine" by isoelectric focusing

A possibility to fractionate fibrinolytically and thrombolytically active complex "tricholysin" into five components, differing in iso-points and in enzymatic activity, is demonstrated by means of isoelectric focusing using ampholine solution within pH range 3.0-10.0. Homogenous fraction IV (isopoint 6.8-7.0) has a low caseinolytic activity and a high specific fibrinolytic and esterase activities. This fraction is characterized with a high ability of plasminogen activation. Serine, threonine, alanine and valine are found to prevail in amino acid composition of the fraction IV, its molecular weight being 39000.