Transformed epithelial cells and fibroblasts/myofibroblasts interaction in breast tumor: a mathematical model and experiments

It is well known that tumor and its microenvironment, or stroma, interact with each other and that this interaction plays a critical role in tumor initiation, growth, and metastasis. This interaction consists of complex relations between tumor cells, stromal cells such as fibroblasts, epithelial cells and immunocytes, the vascular system, the extracellular matrix, and cytokines secreted by the cells. Understanding these relationships may lead to new therapeutic approaches to cancer. In the present paper, we consider tumor-stroma crosstalk in a simple in vitro situation which involves interaction between tumor epithelial cells from breast cancer and a microenvironment consisting of just fibroblasts. The two populations of cells are separated by a semi-permeable membrane that allows only cytokines to cross over. We develop a mathematical model that includes two critical growth factors: TGF-β, produced by the tumor cells, and EGF, secreted by the fibroblasts. The TGF-β modifies the microenvironment by transforming fibroblasts into myofibroblasts. Myofibroblasts secrete higher concentrations of EGF than fibroblasts, thereby, increasing the proliferation of tumor cells. Thus already in this simple setup one sees a mutual interaction between tumor cells and their microenvironment. We conducted experiments which show good agreement with the model’s simulations, hence confirming the model’s ability to predict aspects of tumor cell behavior in response to signaling from fibroblasts.     

Genetic analysis of resistance to blackspot (Diplocarpon rosae) in tetraploid roses

  Diplocarpon rosae is the causal agent of rose blackspot, one of the most severe diseases of field-grown roses. The genetics of resistance to this pathogen was investigated in crosses between tetraploid rose genotypes. The hybrid breeding line 91/100-5, which exhibits a broad resistance to all isolates tested so far, was selfed to produce an F₂ population, backcrossed to the susceptible tetraploid variety ‘Caramba’ and crossed to the susceptible varieties ‘Heckenzauber’, ‘Pariser Charme’ and ‘Elina’. Infection experiments resulted in segregation ratios consistent with the presence of a single dominant resistance locus in the duplex configuration in the hybrid 91/100-5. This suggests, together with previous data on the race structure of the fungus, a “gene-for-gene” type of interaction in the pathosystem Diplocarpon/Rosa. We propose to designate this gene Rdr1, which is the first resistance gene described in the genus Rosa. The advantages and limitations of such an interaction type for future rose breeding programmes and for marker-assisted selection strategies are discussed. Received: 29 August 1997 / Accepted: 19 September 1997     

Reciprocity in play,grooming, and proximity in sibling and nonsibling young rhesus monkeys

Play, grooming, and proximity, and the degree to which these were reciprocated between pairs, were studied in immature sibling and nonsibling rhesus monkeys (Macaca mulatta)in four established captive groups over two seasons. “Interaction reciprocity” and “partner reciprocity” were assessed for each dyad for each of the three behaviors. In play, interaction reciprocity was based on the ratio between the play initiations by each dyad member,in grooming on the ratio between the grooming durations by each dyad member, and in proximity on the relative responsibility for proximity maintenance. Two or three most frequent (top) partners for each behavior were found for each individual. If two monkeys were among each other’s top partners, they were said to be reciprocal partners. Monkeys played with nonsiblings as much as with siblings but spent more time grooming and in proximity with siblings than with nonsiblings. Same-age nonsiblings (peers) were more frequent partners than other nonsiblings for each behavior. Siblings’ grooming interactions were more reciprocal than those of nonsiblings. There was no such effect for play and proximity. All-male dyads tended to be more reciprocal in play interactions, and all-female dyads tended to be more reciprocal in grooming interactions. In play, but not in grooming or proximity, the interaction reciprocity of reciprocal partners was higher than that of nonreciprocal dyads. It is argued that the three behaviors have similar roles in infant’s social development but they differ in the expression of this role. Hence the reciprocity patterns vary with the behavior.     

Analysis of insect toxin complex gene variability of <Emphasis Type="Italic">Yersinia pestis</Emphasis> and <Emphasis Type="Italic">Yersinia pseudotuberculosis</Emphasis> strains

The nucleotide sequences of the Tc’s insect toxin complex genes have been analyzed in 18 natural strains of the main and non-main subspecies of Yersinia pestis isolated in different natural foci in the Russian Federation, as well as neighboring and more remote countries, as compared to the data on Y. pestis and Y. pseudotuberculosis strains stored in the NCBI GenBank database. The nucleotide sequences of these genes in plague agent strains have been found to be highly conserved, in contrast to those of the pseudotuberculosis agent. The sequences of two genes, tcaC and tccC2, have been found to be almost identical in Y. pestis strains, whereas other three genes (tcaA, tcaB, and tccC1) contain a few mutations, which, however, are not common for all strains of the plague agent. Exceptions are only strains of the Y. pestis biovar orientalis, whose tcaB gene is in a nonfunctional state due to a nucleotide deletion. The results suggest that the formation of the species Y. pestis as an agent of a natural focal infection with a transmissive mechanism has not resulted in degradation of the Tc’s complex genes. Instead, these genes are likely to have been altered as the plague agent have been adapting to the new environment.     

On the reciprocal interaction between believing and feeling: an adaptive agent modelling perspective

An agent’s beliefs usually depend on informational or cognitive factors such as observation or received communication or reasoning, but also affective factors may play a role. In this paper, by adopting neurological theories on the role of emotions and feelings, an agent model is introduced incorporating the interaction between cognitive and affective factors in believing. The model describes how the strength of a belief may not only depend on information obtained, but also on the emotional responses on the belief. For feeling emotions a recursive body loop between preparations for emotional responses and feelings is assumed. The model introduces a second feedback loop for the interaction between feeling and belief. The strength of a belief and of the feeling both result from the converging dynamic pattern modelled by the combination of the two loops. For some specific cases it is described, for example, how for certain personal characteristics an optimistic world view is generated in the agent’s beliefs, or, for other characteristics, a pessimistic world view. Moreover, the paper shows how such affective effects on beliefs can emerge and become stronger over time due to experiences obtained. It is shown how based on Hebbian learning a connection from feeling to belief can develop. As these connections affect the strenghts of future beliefs, in this way an effect of judgment ‘by experience built up in the past’ or ‘by gut feeling’ can be obtained. Some example simulation results and a mathematical analysis of the equilibria are presented.     

Upset in response to a Sibling’s partner’s infidelities

Using data collected from people with at least one brother and one sister, and consistent with an evolutionary perspective, we find that older men and women (a) are more upset by a brother’s partner’s sexual infidelity than by her emotional infidelity and (b) are more upset by a sister’s partner’s emotional infidelity than by his sexual infidelity. There were no effects of participant sex or sex of in-law on upset over a sibling’s partner’s infidelities, but there was an effect of participant sex on reports of upset over one’s own partner’s infidelities. The results suggest that the key variable among older participants is the sex of the sibling or, correspondingly, the sex of the sibling’s partner, as predicted from an evolutionary analysis of reproductive costs, and not the sex of the participant, as predicted from a socialization perspective. Discussion offers directions for future work on jealousy.     

Resistance to Phytophthora fragariae var. fragariae in strawberry: the Rpf2 gene

  Phytophthora fragariae var. fragariae is the causal agent of red stele (red core) root rot in strawberry (Fragaria spp.). The inheritance of resistance to one isolate of this fungus was studied in 12 segregating populations of F.×ananassa derived from crosses between four resistant cultivars (‘Climax’, ‘Redgauntlet’, ‘Siletz’, and ‘Sparkle’) and three susceptible cultivars (‘Blakemore’, ‘Glasa’, and ‘Senga’ Sengana’). The analysis clearly supports the hypothesis of a single segregating dominant resistance gene. It is proposed that this gene be designated Rpf2. Received 12 November 1996 / Accepted: 22 November 1996     

Culture–area relation in Axelrod’s model for culture dissemination

Axelrod’s model for culture dissemination offers a nontrivial answer to the question of why there is cultural diversity given that people’s beliefs have a tendency to become more similar to each other’s as they interact repeatedly. The answer depends on the two control parameters of the model, namely, the number F of cultural features that characterize each agent, and the number q of traits that each feature can take on, as well as on the size A of the territory or, equivalently, on the number of interacting agents. Here, we investigate the dependence of the number C of distinct coexisting cultures on the area A in Axelrod’s model, the culture–area relationship, through extensive Monte Carlo simulations. We find a non-monotonous culture–area relation, for which the number of cultures decreases when the area grows beyond a certain size, provided that q is smaller than a threshold value q _c = q _c (F) and F ≥ 3. In the limit of infinite area, this threshold value signals the onset of a discontinuous transition between a globalized regime marked by a uniform culture (C = 1), and a completely polarized regime where all C = q ^F possible cultures coexist. Otherwise, the culture–area relation exhibits the typical behavior of the species–area relation, i.e., a monotonically increasing curve the slope of which is steep at first and steadily levels off at some maximum diversity value.     

Behavioral mechanisms of collective nest-site choice by the ant Temnothorax curvispinosus

This paper examines the individual behavior underlying collective choice among nest sites by the ant Temnothorax (formerly Leptothorax) curvispinosus. Colonies can actively compare options, rejecting a mediocre site when it is paired with a good one, but accepting the same mediocre design if it is instead paired with a worse site. This ability emerges from the behavior of an active minority of workers who organize emigrations. When one of these finds a promising site, she recruits nest mates to it, but only after a delay that varies inversely with site quality. Ants first recruit fellow active ants via slow tandem runs, but eventually switch to speedier transports of the colony’s passive majority. Later transports grow faster still, as ants improve their speed with experience. An ant’s choice of recruitment type is governed by a quorum rule, such that her likelihood of starting to transport increases with the population of the new site. The size of the quorum depends on experience, with ants demanding a larger population to launch immediately into transport than they do to switch to transport after first leading a few tandem runs. Perception of quorum attainment requires direct contact between ants. The ants’ behavior qualitatively matches that of T. albipennis, where models have shown that decentralized choice of the best site depends on quality-dependent recruitment delays, amplified by a quorum rule for initiating transport. Parameter estimates for an agent-based model show significant quantitative differences between the species, and suggest that T. albipennis may place relatively greater emphasis on emigration speed. Received 11 February 2005; revised 10 May 2005; accepted 20 May 2005.     

Copper ions influence the toxicity of β-amyloid(1–42) in a concentration-dependent manner in a <Emphasis Type="Italic">Caenorhabditis elegans</Emphasis> model of Alzheimer’s disease

β-amyloid (Aβ) and copper play important roles in the pathogenesis of Alzheimer’s disease (AD). However, the behavioral correlativity and molecular mechanisms of Aβ and copper toxicity have been investigated less often. In the present study, we investigated the interaction and toxicity of Aβ1–42 and copper in the Aβ1–42 transgenic Caenorhabditis elegans worm model CL2006. Our data show that the paralysis behavior of CL2006 worms significantly deteriorated after exposure to 10⁻³ mol L⁻¹ copper ions. However, the paralysis behavior was dramatically attenuated with exposure to 10⁻⁴ mol L⁻¹ copper ions. The exogenous copper treatment also partially changed the homeostatic balance of zinc, manganese, and iron. Our data suggest that the accumulation of reactive oxygen species (ROS) was responsible for the paralysis induced by Aβ and copper in CL2006. The ROS generation induced by Aβ and copper appear to be through sod-1, prdx-2, skn-1, hsp-60 and hsp-16.2 genes.     

Computing parametric beta diversity with unequal plot weights: a solution based on resampling methods

Jost (Ecology, 88:2427–2439, 2007) recently showed that the Shannon diversity is the only standard diversity measure that can be partitioned into meaningful independent alpha and beta components when plot weights are unequal. This conclusion is very disappointing if one wants to calculate the beta diversity of unequal weighted plots using a parametric measure with varying sensitivities to the occurrence of rare and abundant species. To overcome this impasse, at least partially, in this paper, I propose a parametric measure of beta diversity that is based on the combination of Shannon’s entropy with Hurlbert’s ‘expected species diversity’. Unlike most parametric measures of diversity, the proposed index has a clear probabilistic interpretation, allowing at the same time a multiplicative partition of diversity into independent alpha and beta components for unequally weighted plots.     

An <Emphasis Type="Italic">in vitro</Emphasis> method to evaluate grapevine cultivars for <Emphasis Type="Italic">Erysiphe necator</Emphasis> susceptibility

Powdery mildew, caused by the obligate biotrophic ascomycete Erysiphe necator, is one of the most destructive grapevine diseases worldwide. Cultivars of Vitis vinifera L, for wine and table grape production, are all susceptible to E. necator, whose attacks result in severe epidemics under the warm and dry conditions of the Mediterranean basin. The aim of the present study was to compare the susceptibility of different grapevine cultivars to E. necator by an in vitro assay for assessing the potentiality of this method in breeding programs for resistance to the pathogen. Leaves of 12 grapevine cultivars were spot-inoculated in vitro with about 10 conidia from five different isolates of E. necator, using colony growth and conidiation 3 wk post-inoculation as indicators of susceptibility to the disease. A remarkable difference was observed between highly susceptible cultivars like ‘Baresana’, ‘Malvasia’, ‘Bianca’, and ‘Italia’, and the less susceptible ‘Alphonse Lavallée’ and ‘Ohanez’, in accordance with their behavior in the field. No statistically significant differences were found in the virulence of E. necator isolates.     

��Unfit for Life��: A Case Study of Protector-Protected Analogies in Recent Advocacy of Eugenics and Coercive Genetic Discrimination

This paper utilizes Iris Marion Young’s critical, post-9/11 reading of Thomas Hobbes, “as a theorist of authoritarian government grounded in fear of threat” (Young 2003). Applying Young’s reading of Hobbes to the high-profile ethicist Julian Savulescu’s advocacy of genetic enhancement reveals an underlying unjust discrimination in Savulescu’s use of patriarchal protector–protected analogies between family and state. First, the paper shows how Savulescu’s concept of procreative beneficence, in which parents use genetic selection to have children who will have the “best lives” possible, is unjustly discriminatory against marginalized groups. Increasingly, however, he has invoked public security to justify genetic interventions. In recent speeches, Savulescu has argued a global state of emergency is developing due to a combination of the global environmental crisis, the threat of bioterrorism, and the failure of liberalism. To help deal with this emerging state of emergency, Savulescu advocates an unjustly discriminatory array of genetic-based governance practices, including detention and segregation.     

Modeling Vortex Swarming In Daphnia

Based on experimental observations in Daphnia, we introduce an agent-based model for the motion of single and swarms of animals. Each agent is described by a stochastic equation that also considers the conditions for active biological motion. An environmental potential further reflects local conditions for Daphnia, such as attraction to light sources. This model is sufficient to describe the observed cycling behavior of single Daphnia. To simulate vortex swarming of many Daphnia, i.e. the collective rotation of the swarm in one direction, we extend the model by considering avoidance of collisions. Two different ansatzes to model such a behavior are developed and compared. By means of computer simulations of a multi-agent system we show that local avoidance—as a special form of asymmetric repulsion between animals—leads to the emergence of a vortex swarm. The transition from uncorrelated rotation of single agents to the vortex swarming as a function of the swarm size is investigated. Eventually, some evidence of avoidance behavior in Daphnia is provided by comparing experimental and simulation results for two animals.     

The doctrine of signatures in present-day Israel

Some evidence of the existence of an ancient pharmacological theory—the Doctrine of Signatures—has been found in the folk medicine of Israel. The research reported 14 plants with folk medicinal uses based on the Doctrine of Signatures categories including: similarity of the plant or plant organ to the damaged human organ (Alhagi maurorum, camel thorn;Astragalus macrocarpus, milk-vetch; andCynoglossum creticum, blue hound’s tongue), similarity to animal shape or behavior (Heliotropium europaeum, European turnsole;Asteriscus spinosus, starwort; andBriza maxima, large quaking grass), similarity of plant color to the color of the disease’s symptoms or the medical phenomena (Rhamnus alaternus, Italian buckthorn;Citrullus colocynthis, bitter gourd; andEcballium elaterium, squirting cucumber), and similarity of plant habitat or characteristic to human features (Parietaria judaica, wall pellitory; andRuta chalepensis, African rue).     

The Instinctual Nation-State: Non-Darwinian Theories,State Science and Ultra-Nationalism in Oka Asajirō’s <Emphasis Type="BoldItalic">Evolution and Human Life</Emphasis>

In his anthology of socio-political essays, Evolution and Human Life, Oka Asajirō (1868–1944), early twentieth century Japan’s foremost advocate of evolutionism, developed a biological vision of the nation-state as super-organism that reflected the concerns and aims of German-inspired Meiji statism and anticipated aspects of radical ultra-nationalism. Drawing on non-Darwinian doctrines, Oka attempted to realize such a fused or organic state by enhancing social instincts that would bind the minzoku (ethnic nation) and state into a single living entity. Though mobilization during the Russo-Japanese War seemed to evince this super-organism, the increasingly contentious and complex society that emerged in the war’s aftermath caused Oka to turn first to Lamarckism and eventually to orthogenesis in the hopes of preserving the instincts needed for a viable nation-state. It is especially in the state interventionist measures that Oka finally came to endorse in order to forestall orthogenetically-driven degeneration that the technocratic proclivities of his statist orientation become most apparent. The article concludes by suggesting that Oka’s emphasis on degeneration, autarkic expansion, and, most especially, totalitarian submersion of individuals into the statist collectivity indicates a complex relationship between his evolutionism and fascist ideology, what recent scholarship has dubbed radical Shinto ultra-nationalism.     

Comparative parasitological examination on sympatric equids in the Great Gobi “B” Strictly Protected Area,Mongolia

The Przewalski’s horse (Equus caballus przewalskii) became extinct in the wild during the 1960s. Based on a successful captive breeding program, Przewalski’s horses were reintroduced to the Great Gobi Part “B” strictly protected area (SPA) in SW Mongolia in the late 1990s. The Asiatic wild ass (Equus hemionus hemionus), Przewalski’s horse, and sometimes domestic horses live sympatricly in the Gobi B SPA. Previously published data demonstrates that, as a result of their different requirements and utilization of the park’s resources, their home-range size and social structure differ. Parasitological examinations in the three equid species show how the factors “home range, social structure, and resource selection” significantly impact parasitic burden. Asiatic wild asses are potentially exposed to a higher risk of parasite re-infection due to their temporal aggregation in very large groups. This study demonstrates a highly significant greater parasite load in the Asiatic wild ass for the majority of parasites evaluated (Dictyocaulus arnfieldi, Trichostrongylus axei, Strongyloides westeri, Parascaris equorum) compared to Przewalski’s horses and domestic horses in the same habitat. Domestic horses had higher parasite loads for eggs of strongylids, eggs of anoplocephalidae, and Eimeria leuckarti. The potential risk of cross infection between sympatric living equids is high, as is the cross infection between ruminants and equids. Furthermore, this study reports for the first time the occurrence of lungworms in free-ranging Przewalski’s horses. Whereas, Asiatic wild asses and Przewalski’s horses seem to cope very well with the sometimes high parasite burden, Mongolian domestic horses manifested typical parasite burden symptoms.     

Amounts and patterns of nucleotide variation within and between two Japanese conifers, sugi (Cryptomeria japonica) and hinoki (Chamaecyparis obtusa) (Cupressaceae sensu lato)

Sugi (Cryptomeria japonica) and hinoki (Chamaecyparis obtusa) are the most important timber species in Japan. To quantify and compare the level of nucleotide variation in these species, we investigated their variation at ten nuclear loci. Average values of nucleotide diversity at synonymous sites (π _SYN) found in sugi and hinoki were 0.0038 and 0.0069, respectively. However, although the average value of nucleotide diversity was higher in hinoki than in sugi, their average values of haplotype diversity were similar. Deviations from the standard neutral model were detected at two loci in hinoki using Tajima’s D, Fay and Wu’s H, and Strobeck’s S statistics, which seem to be due to its historical population structure. Levels of divergence between the two species at synonymous sites of the ten genes ranged from 0.121 to 0.566 (0.28 on average). These values positively correlated with their guanine + cytosine contents at third-codon positions of synonymous sites (%GC3s).     

How Lysenkoism Became Pseudoscience: Dobzhansky to Velikovsky

At some point in America in the 1940s, T. D. Lysenko’s neo-Lamarckian hereditary theories transformed from a set of disputed doctrines into a prime exemplar of “pseudoscience.” This paper explores the context in which this theory acquired this pejorative status by examining American efforts to refute Lysenkoism both before and after the famous August 1948 endorsement of Lysenko’s doctrines by the Stalinist state, with particular attention to the translation efforts of Theodosius Dobzhansky. After enumerating numerous tactics for combating perceived pseudoscience, the Lysenko case is then juxtaposed with another American case of alleged pseudoscience: the notorious 1950 scandal surrounding Immanuel Velikovsky’s Worlds in Collision (1950, Worlds in Collision. New York: Macmillan). On several levels, the characterization of Lysenkoism as pseudoscientific served as a template for casting other rejected theories, including Velikovsky’s, in the same light.